Current Knowledge on Endocrine Disrupting Chemicals (EDCs) from Animal Biology to Humans, from Pregnancy to Adulthood: Highlights from a National Italian Meeting

Maria Elisabeth Street, Sabrina Angelini, Sergio Bernasconi, Ernesto Burgio, Alessandra Cassio, Cecilia Catellani, Francesca Cirillo, Annalisa Deodati, Enrica Fabbrizi, Vassilios Fanos, Giancarlo Gargano, Enzo Grossi, Lorenzo Iughetti, Pietro Lazzeroni, Alberto Mantovani, Lucia Migliore, Paola Palanza, Giancarlo Panzica, Anna Maria Papini, Stefano Parmigiani, Barbara Predieri, Chiara Sartori, Gabriele Tridenti, Sergio Amarri, Maria Elisabeth Street, Sabrina Angelini, Sergio Bernasconi, Ernesto Burgio, Alessandra Cassio, Cecilia Catellani, Francesca Cirillo, Annalisa Deodati, Enrica Fabbrizi, Vassilios Fanos, Giancarlo Gargano, Enzo Grossi, Lorenzo Iughetti, Pietro Lazzeroni, Alberto Mantovani, Lucia Migliore, Paola Palanza, Giancarlo Panzica, Anna Maria Papini, Stefano Parmigiani, Barbara Predieri, Chiara Sartori, Gabriele Tridenti, Sergio Amarri

Abstract

Wildlife has often presented and suggested the effects of endocrine disrupting chemicals (EDCs). Animal studies have given us an important opportunity to understand the mechanisms of action of many chemicals on the endocrine system and on neurodevelopment and behaviour, and to evaluate the effects of doses, time and duration of exposure. Although results are sometimes conflicting because of confounding factors, epidemiological studies in humans suggest effects of EDCs on prenatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility, and on carcinogenesis mainly through epigenetic mechanisms. This manuscript reviews the reports of a multidisciplinary national meeting on this topic.

Keywords: Endocrine Disrupting Chemicals (EDCs); autism; carcinogenesis; epigenetics; fertility; growth; neurodevelopment; obesity; puberty; thyroid function.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Action of EDCs on the HPT Axis. The black arrows indicate the endocrine axis, the red arrows indicate the organs/tissues targeted by the EDCs.
Figure 2
Figure 2
Importance of EDCs driven epigenetic effects during life course and potential consequences across generations according to the Developmental Origins of Health and Disease (DOHaD) theory.

References

    1. Colborn T., vom Saal F.S., Soto A.M. Developmental effects of endocrine-disrupting chemicals in wildlife and humans. Environ. Health Perspect. 1993;101:378–384. doi: 10.1289/ehp.93101378.
    1. Myers J.P., Guillette L.J., Jr., Palanza P., Parmigiani S., Swan S.H., vom Saal F.S. The emerging science of endocrine disruption. In: Ragaini R.C., editor. International Seminars on Planetary Emergencies, 30th Session. World Scientific Publishing; London, UK: 2004. pp. 105–121.
    1. Zoeller R.T., Brown T.R., Doan L.L., Gore A.C., Skakkebaek N.E., Soto A.M., Woodruff T.J., Vom Saal F.S. Endocrine-disrupting chemicals and public health protection: A statement of principles from The Endocrine Society. Endocrinology. 2012;153:4097–4110. doi: 10.1210/en.2012-1422.
    1. Heindel J.J., vom Saal F.S., Blumberg B., Bovolin P., Calamandrei G., Ceresini G., Cohn B.A., Fabbri E., Gioiosa L., Kassotis C., et al. Parma consensus statement on metabolic disruptors. Environ. Health. 2015;14:54. doi: 10.1186/s12940-015-0042-7.
    1. Guillette L.J., Jr., Edwards T.M. Environmental influences on fertility: Can we learn lessons from studies of wildlife? Fertil. Steril. 2008;89:e21–e24. doi: 10.1016/j.fertnstert.2007.12.019.
    1. Guillette L.J., Jr., Gunderson M.P. Alterations in development of reproductive and endocrine systems of wildlife populations exposed to endocrine-disrupting contaminants. Reproduction. 2001;122:857–864. doi: 10.1530/rep.0.1220857.
    1. Vos J.G., Dybing E., Greim H.A., Ladefoged O., Lambré C., Tarazona J.V., Brandt I., Vethaak A.D. Health effects of endocrine-disrupting chemicals on wildlife, with special reference to the European situation. Crit. Rev. Toxicol. 2000;30:71–133. doi: 10.1080/10408440091159176.
    1. Guillette L.J., Jr., Gross T.S., Masson G.R., Matter J.M., Percival H.F., Woodward A.R. Developmental abnormalities of the gonad and abnormal sex hormone concentrations in juvenile alligators from contaminated and control lakes in Florida. Environ. Health Perspect. 1994;102:680–688. doi: 10.1289/ehp.94102680.
    1. Le Blanc G. Steroid hormone-regulated processes in Invertebrates and their Susceptability to Environmental Endocrine disruption. In: Crain A., Guillette L.J. Jr., editors. Environmental Endocrine Disruptors: An Evolutionary Perspective. 1st ed. Taylor and Francis Publ.; London, UK: 1999. pp. 217–226.
    1. Oehlmann J., Schulte-Oehlmann U., Kloas W., Jagnytsch O., Lutz I., Kusk K.O., Wollenberger L., Santos E.M., Paull G.C., Van Look K.J., et al. A critical analysis of the biological impacts of plasticizers on wildlife. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009;364:2047–2062. doi: 10.1098/rstb.2008.0242.
    1. Hutchinson T.H. Reproductive and developmental effects of endocrine disrupters in invertebrates: In vitro and in vivo approaches. Toxicol. Lett. 2002;131:75–81. doi: 10.1016/S0378-4274(02)00046-2.
    1. Hamlin H., Guillette L.J., Jr. Wildlife as sentinels of environmental impacts on reproductive health and fertility. In: Woodruff T., Janssen S., Guillette L.J. Jr., Giudice L., editors. Environmental Impacts on Reproductive Health and Fertility. Cambridge University Press; Cambridge, UK: 2010.
    1. Vom Saal F.S., Taylor J.A., Palanza P., Parmigiani S. New Approaches to Risk Evaluation for Chemicals of Emerging Concern (CECs) that have Endocrine Disrupting Effects. In: Ragaini R.C., editor. Proceedings of the International Seminar on Nuclear War and Planetary Emergencies 44th Session; Erice, Italy. 19–24 August 2011; Hackensack, NJ, USA: London, UK: Singapore: World Scientific Publishers; 2011.
    1. Vom Saal F.S. Triennial Reproduction Symposium: Environmental programming of reproduction during fetal life: Effects of intrauterine position and the endocrine disrupting chemical bisphenol A. J. Anim. Sci. 2016;94:2722–2736. doi: 10.2527/jas.2015-0211.
    1. Parmigiani S., vom Saal F.S., Palanza P., Colborn T. Exposure to very low doses of Endocrine disrupting chemicals (EDCs) during fetal life permanently alters brain development and behavior in animals and humans. In: Ragaini R., editor. International Seminar on Nuclear War and Planetary Emergencies, 27th Session. World Scientific Publishers; Hackensack, NJ, USA: London, UK: Singapore: 2003. pp. 293–308.
    1. Vom Saal F.S. The Intrauterine Position Phenomenon. Reference Module in Biomedical Sciences. [(accessed on 2 January 2018)];2018 Available online: .
    1. Parmigiani S., Palanza P., vom Saal F.S. Ethotoxicology: An evolutionary approach to behavioral toxicology. In: Crain A., Guillette L.J. Jr., editors. Environmental Endocrine Disruptors: An Evolutionary Perspective. 1st ed. Taylor and Francis Publ.; London, UK: 1999. pp. 217–226.
    1. Schug T.T., Johnson A.F., Birnbaum L.S., Colborn T., Guillette L.J., Jr., Crews D.P., Collins T., Soto A.M., Vom Saal F.S., McLachlan J.A., et al. Minireview: Endocrine Disruptors: Past Lessons and Future Directions. Mol. Endocrinol. 2016;30:833–847. doi: 10.1210/me.2016-1096.
    1. Vom Saal F.S., Parmigiani S., Palanza P.L., Everett L.G., Ragaini R. The plastic world: Sources, amounts, ecological impacts and effects on development, reproduction, brain and behavior in aquatic and terrestrial animals and humans. Environ. Res. 2008;108:127–130. doi: 10.1016/j.envres.2008.03.008.
    1. Palanza P., Nagel S., Parmigiani S., vom Saal F.S. Perinatal exposure to endocrine disruptors: Sex, timing and behavioral endpoints. Curr. Opin. Behav. Sci. 2016;7:69–75. doi: 10.1016/j.cobeha.2015.11.017.
    1. Palanza P., Gioiosa L., vom Saal F.S., Parmigiani S. Effects of developmental exposure to bisphenol A on brain and behavior in mice. Environ. Res. 2008;108:150–157. doi: 10.1016/j.envres.2008.07.023.
    1. Braun J.M. Early Life Exposure to Endocrine Disrupting Chemicals and Childhood Obesity and Neurodevelopment. Nat. Rev. Endocrinol. 2017;13:161–173. doi: 10.1038/nrendo.2016.186.
    1. Grandjean P., Landrigan P.J. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014;13:330–338. doi: 10.1016/S1474-4422(13)70278-3.
    1. Horan T.S., Marre A., Hassold T., Lawson C., Hunt P.A. Germline and reproductive tract effects intensify in male mice with successive generations of estrogenic exposure. PLoS Genet. 2017;13:e1006885. doi: 10.1371/journal.pgen.1006885.
    1. Crews D., Gore A.C., Hsu T.S., Dangleben N.L., Spinetta M., Schallert T., Anway M.D., Skinner M.K. Transgenerational epigenetic imprints on mate preference. Proc. Natl. Acad. Sci. USA. 2007;104:5942–5946. doi: 10.1073/pnas.0610410104.
    1. Heindel J.J., Blumberg B., Cave M., Machtinger R., Mantovani A., Mendez M.A., Nadal A., Palanza P., Panzica G., Sargis R., et al. Metabolism disrupting chemicals and metabolic disorders. Reprod. Toxicol. 2017;68:3–33. doi: 10.1016/j.reprotox.2016.10.001.
    1. Wolstenholme J.T., Edwards M., Shetty S.R., Gatewood J.D., Taylor J.A., Rissman E.F., Connelly J.J. Gestational exposure to bisphenol a produces transgenerational changes in behaviors and gene expression. Endocrinology. 2012;153:3828–3838. doi: 10.1210/en.2012-1195.
    1. Chin-Chan M., Navarro-Yepes J., Quintanilla-Vega B. Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases. Front. Cell. Neurosci. 2015;10:124. doi: 10.3389/fncel.2015.00124.
    1. Walker D.M., Gore A.C. Epigenetic impacts of endocrine disruptors in the brain. Front. Neuroendocrinol. 2017;44:1–26. doi: 10.1016/j.yfrne.2016.09.002.
    1. Gioiosa L., Parmigiani S., vom Saal F.S., Palanza P. The Effects of Bisphenol A on Emotional Behavior Depend upon the Timing of Exposure, Age and Gender in Mice. Horm. Behav. 2013;63:598–605. doi: 10.1016/j.yhbeh.2013.02.016.
    1. Kundakovic M., Gudsnuk K., Franks B., Madrid J., Miller R.L., Perera F.P., Champagne F.A. Sex-specific epigenetic disruption and behavioral changes following low-dose in utero bisphenol A exposure. Proc. Natl. Acad. Sci. USA. 2013;110:9956–9961. doi: 10.1073/pnas.1214056110.
    1. Matsuda S., Matsuzawa D., Ishii D., Tomizawa H., Sutoh C., Nakazawa K., Amano K., Sajiki J., Shimizu E. Effects of perinatal exposure to low dose of bisphenol A on anxiety like behavior and dopamine metabolites in brain. Prog. Neuropsychopharmacol. Biol. Psychiatry. 2012;39:273–279. doi: 10.1016/j.pnpbp.2012.06.016.
    1. Xu X., Hong X., Xie L., Li T., Yang Y., Zhang Q., Zhang G., Liu X. Gestational and lactational exposure to bisphenol-A affects anxiety- and depression-like behaviors in mice. Horm. Behav. 2012;62:480–490. doi: 10.1016/j.yhbeh.2012.08.005.
    1. Cox K.H., Gatewood J.D., Howeth C., Rissman E.F. Gestational exposure to bisphenol A and cross-fostering affect behaviors in juvenile mice. Horm. Behav. 2010;58:754–761. doi: 10.1016/j.yhbeh.2010.07.008.
    1. Gioiosa L., Fissore E., Ghirardelli G., Parmigiani S., Palanza P. Developmental exposure to low-dose estrogenic endocrine disruptors alters sex differences in exploration and emotional responses in mice. Horm. Behav. 2007;52:307–316. doi: 10.1016/j.yhbeh.2007.05.006.
    1. Rubin B.S., Lenkowski J.R., Schaeberle C.M., Vandenberg L.N., Ronsheim P.M., Soto A.M. Evidence of altered brain sexual differentiation in mice exposed perinatally to low, environmentally relevant levels of bisphenol A. Endocrinology. 2006;147:3681–3691. doi: 10.1210/en.2006-0189.
    1. Patisaul H.B., Sullivan A.W., Radford M.E., Walker D.M., Adewale H.B., Winnik B., Coughlin J.L., Buckley B., Gore A.C. Anxiogenic effects of developmental bisphenol A exposure are associated with gene expression changes in the juvenile rat amygdala and mitigated by soy. PLoS ONE. 2012;7:e43890. doi: 10.1371/journal.pone.0043890.
    1. Farabollini F., Porrini S., Dessi-Fulgheri F. Perinatal exposure to the estrogenic pollutant bisphenol A affects behavior in male and female rats. Pharmacol. Biochem. Behav. 1999;64:687–694. doi: 10.1016/S0091-3057(99)00136-7.
    1. Jašarević E., Williams S.A., Vandas G.M., Ellersieck M.R., Liao C., Kannan K., Roberts R.M., Geary D.C., Rosenfeld C.S. Sex and dose-dependent effects of developmental exposure to bisphenol A on anxiety and spatial learning in deer mice (Peromyscus maniculatus bairdii) offspring. Horm. Behav. 2013;63:180–189. doi: 10.1016/j.yhbeh.2012.09.009.
    1. Jašarević E., Sieli P.T., Twellman E.E., Welsh T.H., Jr., Schachtman T.R., Roberts R.M., Rosenfeld C.S. Disruption of adult expression of sexually selected traits by developmental exposure to bisphenol A. Proc. Natl. Acad. Sci. USA. 2011;108:11715–11720. doi: 10.1073/pnas.1107958108.
    1. Evans S.F., Kobrosly R.W., Barrett E.S., Thurston S.W., Calafat A.M., Weiss B., Stahlhut R., Yolton K., Swan S.H. Prenatal bisphenol A exposure and maternally reported behavior in boys and girls. Neurotoxicology. 2014;45:91–99. doi: 10.1016/j.neuro.2014.10.003.
    1. Harley K.G., Gunier R.B., Kogut K., Johnson C., Bradman A., Calafat A.M., Eskenazi B. Prenatal and early childhood bisphenol A concentrations and behaviour in school-aged children. Environ. Res. 2013;126:43–50. doi: 10.1016/j.envres.2013.06.004.
    1. Perera F., Vishnevetsky J., Herbstman J.B., Calafat A.M., Xiong W., Rauh V., Wang S. Prenatal bisphenol A exposure and child behavior in an inner-city cohort. Environ. Health Perspect. 2012;120:1190–1194. doi: 10.1289/ehp.1104492.
    1. Braun J.M., Kalkbrenner A.E., Calafat A.M., Yolton K., Ye X., Dietrich K.N., Lanphear B.P. Impact of early-life bisphenol A exposure on behavior and executive function in children. Pediatrics. 2011;128:873–882. doi: 10.1542/peds.2011-1335.
    1. Kuwahara R., Kawaguchi S., Kohara Y., Cui H., Yamashita K. Perinatal exposure to low-dose bisphenol A impairs spatial learning and memory in male rats. J. Pharmacol. 2013;123:132–139. doi: 10.1254/jphs.13093FP.
    1. Kundakovic M., Gudsnuk K., Herbstman J.B., Tang D., Perera F.P., Champagne F.A. DNA methylation of BDNF as a biomarker of early-life adversity. Proc. Natl. Acad. Sci. USA. 2015;112:6807–6813. doi: 10.1073/pnas.1408355111.
    1. Hong S.B., Hong Y.C., Kim J.W., Park E.J., Shin M.S., Kim B.N., Yoo H.J., Cho I.H., Bhang S.Y., Cho S.C. Bisphenol A in relation to behavior and learning of school-age children. J. Child Psychol. Psychiatry. 2013;54:890–899. doi: 10.1111/jcpp.12050.
    1. Maserejian N.N., Trachtenberg F.L., Hauser R., McKinlay S., Shrader P., Bellinger D.C. Dental composite restorations and neuropsychological development in children: Treatment level analysis from a randomized clinical trial. Neurotoxicology. 2012;33:1291–1297. doi: 10.1016/j.neuro.2012.08.001.
    1. Negishi T., Nakagami A., Kawasaki K., Nishida Y., Ihara T., Kuroda Y., Tashiro T., Koyama T., Yoshikawa Y. Altered social interactions in male juvenile cynomolgus monkeys prenatally exposed to bisphenol A. Neurotoxicol. Teratol. 2014;44:46–52. doi: 10.1016/j.ntt.2014.05.004.
    1. Porrini S., Belloni V., Della Seta D., Farabollini F., Giannelli G., Dessì-Fulgheri F. Early exposure to a low dose of bisphenol A affects socio-sexual behavior of juvenile female rats. Brain Res. Bull. 2005;65:261–266. doi: 10.1016/j.brainresbull.2004.11.014.
    1. Jones B.A., Shimell J.J., Watson N.V. Pre- and postnatal bisphenol A treatment results in persistent deficits in the sexual behavior of male rats, but not female rats, in adulthood. Horm. Behav. 2011;59:246–251. doi: 10.1016/j.yhbeh.2010.12.006.
    1. Kobrosly R.W., Evans S., Miodovnik A., Barrett E.S., Thurston S.W., Calafat A.M., Swan S.H. Prenatal phthalate exposures and neurobehavioral development scores in boys and girls at 6–10 years of age. Environ. Health Perspect. 2014;122:521–528. doi: 10.1289/ehp.1307063.
    1. Lien Y.J., Ku H.Y., Su P.H., Chen S.J., Chen H.Y., Liao P.C., Chen W.J., Wang S.L. Prenatal exposure to phthalate esters and behavioral syndromes in children at eight years of age: Taiwan maternal and infant cohort study. Environ. Health Perspect. 2014;123:95–100. doi: 10.1289/ehp.1307154.
    1. Palanza P. The “Plastic” Mother. Endocrinology. 2017;158:461–463. doi: 10.1210/en.2017-00071.
    1. Palanza P., Howdeshell K.L., Parmigiani S., vom Saal F.S. Exposure to a low dose of bisphenol A during fetal life or in adulthood alters maternal behavior in mice. Environ. Health Perspect. 2002;110:415–422. doi: 10.1289/ehp.02110s3415.
    1. Boudalia S., Berges R., Chabanet C., Folia M., Decocq L., Pasquis B., Abdennebi-Najar L., Canivenc-Lavier M.C. A multi-generational study on low-dose BPA exposure in Wistar rats: Effects on maternal behavior, flavor intake and development. Neurotoxicol. Teratol. 2014;41:16–26. doi: 10.1016/j.ntt.2013.11.002.
    1. Della Seta D., Minder I., Dessì-Fulgheri F., Farabollini F. Bisphenol-A exposure during pregnancy and lactation affects maternal behavior in rats. Brain Res. Bull. 2005;65:255–260. doi: 10.1016/j.brainresbull.2004.11.017.
    1. Catanese M.C., Vandenberg LN. Bisphenol S (BPS) Alters Maternal Behavior and Brain in Mice Exposed During Pregnancy/Lactation and Their Daughters. Endocrinology. 2017;158:516–530. doi: 10.1210/en.2016-1723.
    1. Engell M.D., Godwin J., Young L.J., Vandenbergh J.G. Perinatal exposure to endocrine disrupting compounds alters behavior and brain in the female pine vole. Neurotoxicol. Teratol. 2006;28:103–110. doi: 10.1016/j.ntt.2005.10.002.
    1. Johnson S.A., Javurek A.B., Painter M.S., Peritore M.P., Ellersieck M.R., Roberts R.M., Rosenfeld C.S. Disruption of parenting behaviors in california mice, a monogamous rodent species, by endocrine disrupting chemicals. PLoS ONE. 2015;10:e0126284. doi: 10.1371/journal.pone.0126284.
    1. Champagne F.A., Curley J.P. Epigenetic mechanisms mediating the long-term effects of maternal care on development. Neurosci. Biobehav. Rev. 2009;33:593–600. doi: 10.1016/j.neubiorev.2007.10.009.
    1. Panzica G.C., Viglietti-Panzica C., Mura E., Quinn M.J., Jr., Lavoie E., Palanza P., Ottinger M.A. Effects of xenoestrogens on the differentiation of behaviorally-relevant neural circuits. Front. Neuroendocrinol. 2007;28:179–200. doi: 10.1016/j.yfrne.2007.07.001.
    1. Masuo Y., Ishido M. Neurotoxicity of endocrine disruptors: Possible involvement in brain development and neurodegeneration. J. Toxicol. Environ. Health B Crit. Rev. 2011;14:346–369. doi: 10.1080/10937404.2011.578557.
    1. Rosenfeld C.S., Trainor B.C. Environmental Health Factors and Sexually Dimorphic Differences in Behavioral Disruptions. Curr. Environ. Health Rep. 2014;1:287–301. doi: 10.1007/s40572-014-0027-7.
    1. Van Naarden Braun K., Christensen D., Doernberg N., Schieve L., Rice C., Wiggins L., Schendel D., Yeargin-Allsopp M. Trends in the prevalence of autism spectrum disorder, cerebral palsy, hearing loss, intellectual disability, and vision impairment, metropolitan atlanta, 1991–2010. PLoS ONE. 2015;10:e0124120. doi: 10.1371/journal.pone.0124120.
    1. Boyle C.A., Decouflé P., Yeargin-Allsopp M. Prevalence and health impact of developmental disabilities in US children. Pediatrics. 1994;93:399–403.
    1. Lavelle T.A., Weinstein M.C., Newhouse J.P., Munir K., Kuhlthau K.A., Prosser L.A. Economic burden of childhood autism spectrum disorders. Pediatrics. 2014;133:e520–e529. doi: 10.1542/peds.2013-0763.
    1. Lai M.C., Lombardo M.V., Baron-Cohen S. Autism. Lancet. 2014;383:896–910. doi: 10.1016/S0140-6736(13)61539-1.
    1. Grandjean P., Landrigan P.J. Developmental neurotoxicity of industrial chemicals. Lancet. 2006;368:2167–2178. doi: 10.1016/S0140-6736(06)69665-7.
    1. Predki P.F., Sarkar B. Metal replacement in “zinc finger” and its effect on DNA binding. Environ. Health Perspect. 1994;102:195–198. doi: 10.1289/ehp.94102s3195.
    1. Kern J.K., Geier D.A., Sykes L.K., Haley B.E., Geier M.R. The relationship between mercury and autism: A comprehensive review and discussion. J. Trace Elem. Med. Biol. 2016;37:8–24. doi: 10.1016/j.jtemb.2016.06.002.
    1. Mostafa G.A., Bjørklund G., Urbina M.A., Al-Ayadhi L.Y. The levels of blood mercury and inflammatory-related neuropeptides in the serum are correlated in children with autism spectrum disorder. Metab. Brain Dis. 2016;31:593–599. doi: 10.1007/s11011-015-9784-8.
    1. Mostafa G.A., Al-Ayadhi L.Y. The possible association between elevated levels of blood mercury and the increased frequency of serum anti-myelin basic protein auto-antibodies in autistic children. J. Clin. Cell. Immunol. 2015;6:2. doi: 10.4172/2155-9899.1000310.
    1. Sajdel-Sulkowska E.M., Lipinski B., Windom H., Audhya T., McGinnis W. Oxidative stress in autism: Cerebellar 3 nitrotyrosine levels. Am. J. Biochem. Biotechnol. 2008;4:73–84.
    1. Mostafa G.A., Refai T.M.K. Antineuronal antibodies in autistic children: Relation to blood mercury. Egypt. J. Pediatr. Allergy Immunol. 2007;5:21–30.
    1. Geier D.A., Kern J.K., King P.G., Sykes L.K., Geier M.R. A case-control study evaluating the relationship between Thimerosal-containing Haemophilus influenzae Type b vaccine administration and the risk for a pervasive developmental disorder diagnosis in the United States. Biol. Trace Elem. Res. 2015;163:28–38. doi: 10.1007/s12011-014-0169-3.
    1. Geier D.A., Hooker B.S., Kern J.K., King P.G., Sykes L.K., Homme K.G., Geier M.R. A dose-response relationship between organic mercury exposure from Thimerosal-containing vaccines and neurodevelopmental disorders. Int. J. Environ. Res. Public Health. 2014;11:9156–9170. doi: 10.3390/ijerph110909156.
    1. Geier D.A., Kern J.K., King P.G., Sykes L.K., Homme K.G., Geier M.R. The risk of neurodevelopmental disorders following a Thimerosal-preserved DTaP formulation in comparison to its Thimerosal-reduced formulation in the Vaccine Adverse Event Reporting System (VAERS) J. Biochem. Pharmacol. Res. 2014;2:64–73.
    1. Geier D.A., Hooker B.S., Kern J.K., King P.G., Sykes L.K., Geier M.R. A two-phase cohort study of the relationship between Thimerosal-containing vaccine administration as a risk factor for an autism spectrum disorder diagnosis in the United States. Transl. Neurodegener. 2013;2:25. doi: 10.1186/2047-9158-2-25.
    1. Stamova B., Green P.G., Tian Y., Hertz-Picciotto I., Pessah I.N., Hansen R., Yang X., Teng J., Gregg J.P., Ashwood P., et al. Correlations between gene expression and mercury levels in blood of boys with and without autism. Neurotox. Res. 2011;19:31–48. doi: 10.1007/s12640-009-9137-7.
    1. Chauhan A., Audhya T., Chauhan V. Brain region-specific glutathione redox imbalance in autism. Neurochem. Res. 2012;37:1681–1689. doi: 10.1007/s11064-012-0775-4.
    1. Rose S., Wynne R., Frye R.E., Melnyk S., James S.J. Increased susceptibility to ethylmercury-induced mitochondrial dysfunction in a subset of autism lymphoblastoid cell lines. J. Toxicol. 2015;2015:1–13. doi: 10.1155/2015/573701.
    1. James S.J., Melnyk S., Fuchs G., Reid T., Jernigan S., Pavliv O., Hubanks A., Gaylor D.W. Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. Am. J. Clin. Nutr. 2009;89:425–430. doi: 10.3945/ajcn.2008.26615.
    1. James S.J., Melnyk S., Jernigan S., Cleves M.A., Halsted C.H., Wong D.H., Cutler P., Bock K., Boris M., Bradstreet J.J., et al. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am. J. Med. Genet. B Neuropsychiatr. Genet. 2006;141B:947–956. doi: 10.1002/ajmg.b.30366.
    1. Frye R.E., Delatorre R., Taylor H., Slattery J., Melnyk S., Chowdhury N., James S.J. Redox metabolism abnormalities in autistic children associated with mitochondrial disease. Transl. Psychiatry. 2013;3:e273. doi: 10.1038/tp.2013.51.
    1. Gu F., Chauhan V., Chauhan A. Impaired synthesis and antioxidant defense of glutathione in the cerebellum of autistic subjects: Alterations in the activities and protein expression of glutathione-related enzymes. Free Radic. Biol. Med. 2013;65:488–496. doi: 10.1016/j.freeradbiomed.2013.07.021.
    1. Rose S., Melnyk S., Pavliv O., Bai S., Nick T.G., Frye R.E., James S.J. Evidence of oxidative damage and inflammation associated with low glutathione redox status in the autism brain. Transl. Psychiatry. 2012;10:e134. doi: 10.1038/tp.2012.61.
    1. Alabdali A., Al-Ayadhi L., El-Ansary A. A key role for an impaired detoxification mechanism in the etiology and severity of autism spectrum disorders. Behav. Brain Funct. 2014;10:14. doi: 10.1186/1744-9081-10-14.
    1. Adams J.B., Audhya T., McDonough-Means S., Rubin R.A., Quig D., Geis E., Gehn E., Loresto M., Mitchell J., Atwood S., et al. Toxicological status of children with autism vs. neurotypical children and the association with autism severity. Biol. Trace Elem. Res. 2013;151:171–180. doi: 10.1007/s12011-012-9551-1.
    1. Lakshmi Priya M.D., Geetha A. Level of trace elements (copper, zinc, magnesium and selenium) and toxic elements (lead and mercury) in the hair and nail of children with autism. Biol. Trace Elem. Res. 2011;142:148–158. doi: 10.1007/s12011-010-8766-2.
    1. Woods J.S., Armel S.E., Fulton D.I., Allen J., Wessels K., Simmonds P.L., Granpeesheh D., Mumper E., Bradstreet J.J., Echeverria D., et al. Urinary porphyrin excretion in neurotypical and autistic children. Environ. Health Perspect. 2010;118:1450–1457. doi: 10.1289/ehp.0901713.
    1. Geier D.A., Kern J.K., Geier M.R. A prospective blinded evaluation of urinary porphyrins verses the clinical severity of autism spectrum disorders. J. Toxicol. Environ. Health Part A. 2009;72:1585–1591. doi: 10.1080/15287390903232475.
    1. Blanchard K.S., Palmer R.F., Stein Z. The value of ecologic studies: Mercury concentration in ambient air and the risk of autism. Rev. Environ. Health. 2011;26:111–118. doi: 10.1515/reveh.2011.015.
    1. Dickerson A.S., Rahbar M.H., Han I., Bakian A.V., Bilder D.A., Harrington R.A., Pettygrove S., Durkin M., Kirby R.S., Wingate M.S., et al. Atism spectrum disorder prevalence and proximity to industrial facilities releasing arsenic, lead or mercury. Sci. Total Environ. 2015;536:245–251. doi: 10.1016/j.scitotenv.2015.07.024.
    1. Lyall K., Croen L.A., Sjödin A., Yoshida C.K., Zerbo O., Kharrazi M., Windham G.C. Polychlorinated Biphenyl and Organochlorine Pesticide Concentrations in Maternal Mid-Pregnancy Serum Samples: Association with Autism Spectrum Disorder and Intellectual Disability. Environ. Health Perspect. 2017;125:474–480. doi: 10.1289/EHP277.
    1. Volk H.E., Lurmann F., Penfold B., Hertz-Picciotto I., McConnell R. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013;70:71–77. doi: 10.1001/jamapsychiatry.2013.266.
    1. Volk H.E., Hertz-Picciotto I., Delwiche L., Lurmann F., McConnell R. Residential proximity to freeways and autism in the CHARGE study. Environ. Health Perspect. 2011;119:873–877. doi: 10.1289/ehp.1002835.
    1. Frederiksen M., Vorkamp K., Thomsen M., Knudsen L.E. Human internal and external exposure to PBDEs—A review of levels and sources. Int. J. Hyg. Environ. Health. 2009;212:109–134. doi: 10.1016/j.ijheh.2008.04.005.
    1. Vuong A.M., Yolton K., Dietrich K.N., Braun J.M., Lanphear B.P., Chen A. Exposure to polybrominated diphenyl ethers (PBDEs) and child behavior: Current findings and future directions. Horm. Behav. 2017;101:94–104. doi: 10.1016/j.yhbeh.2017.11.008.
    1. Jeddi M.Z., Janani L., Memari A.H., Akhondzadeh S., Yunesian M. The role of phthalate esters in autism development: A systematic review. Environ. Res. 2016;151:493–504. doi: 10.1016/j.envres.2016.08.021.
    1. Stein T.P., Schluter M.D., Steer R.A., Guo L., Ming X. Bisphenol A Exposure in Children with Autism Spectrum Disorders. Autism Res. 2015;8:272–283. doi: 10.1002/aur.1444.
    1. Shelton J.F., Geraghty E.M., Tancredi D.J., Delwiche L.D., Schmidt R.J., Ritz B., Hansen R.L., Hertz-Picciotto I. Neurodevelopmental disorders and prenatal residential proximity to agricultural pesticides: The CHARGE study. Environ. Health Perspect. 2014;122:1103–1109. doi: 10.1289/ehp.1307044.
    1. Grün F., Blumberg B. Environmental obesogens: Organotins and endocrine disruption via nuclear receptor signaling. Endocrinology. 2006;147:S50–S55. doi: 10.1210/en.2005-1129.
    1. Angle B.M., Do R.P., Ponzi D., Stahlhut R.W., Drury B.E., Nagel S.C., Welshons W.V., Besch-Williford C.L., Palanza P., Parmigiani S., et al. Metabolic disruption in male mice due to fetal exposure to low but not high doses of bisphenol A (BPA): Evidence for effects on body weight, food intake, adipocytes, leptin, adiponectin, insulin and glucose regulation. Reprod. Toxicol. 2013;42:256–268. doi: 10.1016/j.reprotox.2013.07.017.
    1. Palmer B.F., Clegg D.J. The sexual dimorphism of obesity. Mol. Cell. Endocrinol. 2015;402:113–119. doi: 10.1016/j.mce.2014.11.029.
    1. Valassi E., Scacchi M., Cavagnini F. Neuroendocrine control of food intake. Nutr. Metab. Cardiovasc. Dis. 2008;18:158–168. doi: 10.1016/j.numecd.2007.06.004.
    1. Kalra S.P., Dube M.G., Pu S., Xu B., Horvath T.L., Kalra P.S. Interacting appetite-regulating pathways in the hypothalamic regulation of body weight. Endocr. Rev. 1999;20:68–100. doi: 10.1210/er.20.1.68.
    1. Baskin D.G., Figlewicz Lattemann D., Seeley R.J., Woods S.C., Porte D., Jr., Schwartz M.W. Insulin and leptin: Dual adiposity signals to the brain for the regulation of food intake and body weight. Brain Res. 1999;848:114–123. doi: 10.1016/S0006-8993(99)01974-5.
    1. Grill H.J., Kaplan J.M. The neuroanatomical axis for control of energy balance. Front. Neuroendocrinol. 2002;23:2–40. doi: 10.1006/frne.2001.0224.
    1. Joseph-Bravo P., Jaimes-Hoy L., Charli J.L. Regulation of TRH neurons and energy homeostasis-related signals under stress. J. Endocrinol. 2015;224:R139–R159. doi: 10.1530/JOE-14-0593.
    1. Shi H., Strader A.D., Sorrell J.E., Chambers J.B., Woods S.C., Seeley R.J. Sexually different actions of leptin in proopiomelanocortin neurons to regulate glucose homeostasis. Am. J. Physiol. Endocrinol. Metab. 2008;294:E630–E639. doi: 10.1152/ajpendo.00704.2007.
    1. Bo E., Farinetti A., Marraudino M., Sterchele D., Eva C., Gotti S., Panzica G.C. Adult exposure to tributyltin affects hypothalamic neuropeptide Y, Y1 receptor distribution, and circulating leptin in mice. Andrology. 2016;4:723–734. doi: 10.1111/andr.12222.
    1. Martini M., Sica M., Gotti S., Eva C., Panzica G.C. Effects of estrous cycle and sex on the expression of neuropeptide Y Y1 receptor in discrete hypothalamic and limbic nuclei of transgenic mice. Peptides. 2011;32:1330–1334. doi: 10.1016/j.peptides.2011.04.004.
    1. Clegg D.J., Brown L.M., Woods S.C., Benoit S.C. Gonadal hormones determine sensitivity to central leptin and insulin. Diabetes. 2006;55:978–987. doi: 10.2337/diabetes.55.04.06.db05-1339.
    1. Walley S.N., Roepke T.A. Perinatal exposure to endocrine disrupting compounds and the control of feeding behavior-An overview. Horm. Behav. 2017;101:22–28. doi: 10.1016/j.yhbeh.2017.10.017.
    1. Mackay H., Patterson Z., Khazall R., Patel S., Tsirlin D., Abizaid A. Organizational effects of perinatal exposure to bisphenol-A and diethylstilbestrol on arcuate nucleus circuitry controlling food intake and energy expenditure in male and female CD-1 mice. Endocrinology. 2013;154:1465–1475. doi: 10.1210/en.2012-2044.
    1. Grun F. The obesogen tributyltin. Vitam. Horm. 2014;94:277–325. doi: 10.1016/B978-0-12-800095-3.00011-0.
    1. Decherf S., Demeneix B.A. The obesogen hypothesis: A shift of focus from the periphery to the hypothalamus. J. Toxicol. Environ. Health B Crit. Rev. 2011;14:423–448. doi: 10.1080/10937404.2011.578561.
    1. Decherf S., Seugnet I., Fini J.B., Clerget-Froidevaux M.S., Demeneix B.A. Disruption of thyroid hormone-dependent hypothalamic set-points by environmental contaminants. Mol. Cell. Endocrinol. 2010;323:172–182. doi: 10.1016/j.mce.2010.04.010.
    1. Bo E., Viglietti-Panzica C., Panzica G.C. Acute exposure to tributyltin induces c-fos activation in the hypothalamic arcuate nucleus of adult male mice. Neurotoxicology. 2011;32:277–280. doi: 10.1016/j.neuro.2010.12.011.
    1. Farinetti A., Marraudino M., Ponti G., Gotti S., Panzica G.C. Sexually dimorphic effect of chronic treatment with tributyltin on brain circuits involved in the food intake behavior in adult mice. In: Gotti S., Panzica G.C., editors. 9th International Meeting Steroids and Nervous System. Fondazione Cavalieri Ottolenghi; Torino, Italy: 2017. p. 58.
    1. He K., Zhang J., Chen Z. Effect of tributyltin on the food intake and brain neuropeptide expression in rats. Endokrynol. Polska. 2014;65:485–490. doi: 10.5603/EP.2014.0068.
    1. Merlo E., Podratz P.L., Sena G.C., de Araujo J.F., Lima L.C., Alves I.S., Gama-de-Souza L.N., Pelicao R., Rodrigues L.C., Brandao P.A., et al. The Environmental Pollutant Tributyltin Chloride Disrupts the Hypothalamic-Pituitary-Adrenal Axis at Different Levels in Female Rats. Endocrinology. 2016;157:2978–2995. doi: 10.1210/en.2015-1896.
    1. Sarruf D.A., Yu F., Nguyen H.T., Williams D.L., Printz R.L., Niswender K.D., Schwartz M.W. Expression of peroxisome proliferator-activated receptor-gamma in key neuronal subsets regulating glucose metabolism and energy homeostasis. Endocrinology. 2009;150:707–712. doi: 10.1210/en.2008-0899.
    1. Tontonoz P., Spiegelman B.M. Fat and beyond: The diverse biology of PPARgamma. Annu. Rev. Biochem. 2008;77:289–312. doi: 10.1146/annurev.biochem.77.061307.091829.
    1. Evans R.M., Barish G.D., Wang Y.X. PPARs and the complex journey to obesity. Nat. Med. 2004;10:355–361. doi: 10.1038/nm1025.
    1. Tontonoz P., Hu E., Spiegelman B.M. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 1994;79:1147–1156. doi: 10.1016/0092-8674(94)90006-X.
    1. Yin L., Yu K.S., Lu K., Yu X. Benzyl butyl phthalate promotes adipogenesis in 3T3-L1 preadipocytes: A High Content Cellomics and metabolomic analysis. Toxicol. In Vitro. 2016;32:297–309. doi: 10.1016/j.tiv.2016.01.010.
    1. Pereira-Fernandes A., Demaegdt H., Vandermeiren K., Hectors TL., Jorens PG., Blust R., Vanparys C. Evaluation of a screening system for obesogenic compounds: Screening of endocrine disrupting compounds and evaluation of the PPAR dependency of the effect. PLoS ONE. 2013;8:e77481. doi: 10.1371/journal.pone.0077481.
    1. Arsenescu V., Arsenescu R.I., King V., Swanson H., Cassis L.A. Polychlorinated biphenyl-77 induces adipocyte differentiation and proinflammatory adipokines and promotes obesity and atherosclerosis. Environ. Health Perspect. 2008;116:761–768. doi: 10.1289/ehp.10554.
    1. Rönn M., Lind L., Örberg J., Kullberg J., Söderberg S., Larsson A., Johansson L., Ahlström H., Lind P.M. Bisphenol A is related to circulating levels of adiponectin, leptin and ghrelin, but not to fat mass or fat distribution in humans. Chemosphere. 2014;112:42–48. doi: 10.1016/j.chemosphere.2014.03.042.
    1. Polyzos S.A., Kountouras J., Deretzi G., Zavos C., Mantzoros C.S. The emerging role of endocrine disruptors in pathogenesis of insulin resistance: A concept implicating nonalcoholic fatty liver disease. Curr. Mol. Med. 2012;12:68–82. doi: 10.2174/156652412798376161.
    1. O’Reilly M.W., House P.J., Tomlinson J.W. Understanding androgen action in adipose tissue. J. Steroid. Biochem. Mol. Biol. 2014;143:277–284. doi: 10.1016/j.jsbmb.2014.04.008.
    1. Isidori A.M., Giannetta E., Greco E.A., Gianfrilli D., Bonifacio V., Isidori A., Lenzi A., Fabbri A. Effects of testosterone on body composition, bone metabolism and serum lipid profile in middle-aged men: A meta-analysis. Clin. Endocrinol. 2005;63:280–293. doi: 10.1111/j.1365-2265.2005.02339.x.
    1. Darbre P.D. Endocrine Disruptors and Obesity. Curr. Obes. Rep. 2017;6:18–27. doi: 10.1007/s13679-017-0240-4.
    1. Williams G. Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-α and GPER signalling. Mol. Cell. Endocrinol. 2012;351:269–278. doi: 10.1016/j.mce.2011.12.017.
    1. Lottrup G., Andersson A.M., Leffers H., Mortensen G.K., Toppari J., Skakkebaek N.E., Main K.M. Possible impact of phthalates on infant reproductive health. Int. J. Androl. 2006;29:172–180. doi: 10.1111/j.1365-2605.2005.00642.x.
    1. McAninch E.A., Bianco A.C. Thyroid hormone signaling in energy homeostasis and energy metabolism. Ann. N. Y. Acad. Sci. 2014;1311:77–87. doi: 10.1111/nyas.12374.
    1. Santos-Silva A.P., Andrade M.N., Pereira-Rodrigues P., Paiva-Melo F.D., Soares P., Graceli J.B., Dias G.R.M., Ferreira A.C.F., de Carvalho D.P., Miranda-Alves L. Frontiers in endocrine disruption: Impacts of organotin on the hypothalamus-pituitary-thyroid axis. Mol. Cell. Endocrinol. 2018;460:246–257. doi: 10.1016/j.mce.2017.07.038.
    1. Geens T., Dirtu A.C., Dirinck E., Malarvannan G., Van Gaal L., Jorens P.G., Covaci A. Daily intake of bisphenol A and triclosan and their association with anthropometric data, thyroidhormones and weight loss in overweight and obese individuals. Environ. Int. 2015;76:98–105. doi: 10.1016/j.envint.2014.12.003.
    1. Le Corre L., Besnard P., Chagnon M.C. BPA, an energy balance disruptor. Crit. Rev. Food. Sci. Nutr. 2015;55:769–777. doi: 10.1080/10408398.2012.678421.
    1. Petrakis D., Vassilopoulou L., Mamoulakis C., Psycharakis C., Anifantaki A., Sifakis S., Docea A.O., Tsiaoussis J., Makrigiannakis A., Tsatsakis A.M. Endocrine Disruptors Leading to Obesity and Related Diseases. Int. J. Environ. Res. Public Health. 2017;14:1282. doi: 10.3390/ijerph14101282.
    1. Snedeker S.M., Hay A.G. Do interactions between gut ecology and environmental chemicals contribute to obesity and diabetes? Environ. Health Perspect. 2012;120:332–339. doi: 10.1289/ehp.1104204.
    1. Zhang L., Nichols R.G., Correll J., Murray I.A., Tanaka N., Smith P.B., Hubbard T.D., Sebastian A., Albert I., Hatzakis E., et al. Persistent Organic Pollutants Modify Gut Microbiota-Host Metabolic Homeostasis in Mice through Aryl Hydrocarbon Receptor Activation. Environ. Health Perspect. 2015;123:679–688. doi: 10.1289/ehp.1409055.
    1. Neel B.A., Sargis R.M. The paradox of progress: Environmental disruption of metabolism and the diabetes epidemic. Diabetes. 2011;60:1838–1848. doi: 10.2337/db11-0153.
    1. Zuo Z., Wu T., Lin M., Zhang S., Yan F., Yang Z., Wang Y., Wang C. Chronic exposure to tributyltin chloride induces pancreatic islet cell apoptosis and disrupts glucose homeostasis in male mice. Environ. Sci. Technol. 2014;48:5179–5186. doi: 10.1021/es404729p.
    1. Lin Y., Wei J., Li Y., Chen J., Zhou Z., Song L., Wei Z., Lv Z., Chen X., Xia W., et al. Developmental exposure to di(2-ethylhexyl) phthalate impairs endocrine pancreas and leads to long-term adverse effects on glucose homeostasis in the rat. Am. J. Physiol. Endocrinol. Metab. 2011;301:E527–E538. doi: 10.1152/ajpendo.00233.2011.
    1. Soriano S., Alonso-Magdalena P., García-Arévalo M., Novials A., Muhammed S.J., Salehi A., Gustafsson J.A., Quesada I., Nadal A. Rapid insulinotropic action of low doses of bisphenol-A on mouse and human islets of Langerhans: Role of estrogen receptor β. PLoS ONE. 2012;7:e31109. doi: 10.1371/journal.pone.0031109.
    1. Perreault L., McCurdy C., Kerege A.A., Houck J., Færch K., Bergman B.C. Bisphenol A impairs hepatic glucose sensing in C57BL/6 male mice. PLoS ONE. 2013;8:e69991. doi: 10.1371/journal.pone.0069991.
    1. Manikkam M., Tracey R., Guerrero-Bosagna C., Skinner M.K. Plastics derived endocrine disruptors (BPA, DEHP and DBP) induce epigenetic transgenerational inheritance of obesity, reproductive disease and sperm epimutations. PLoS ONE. 2013;8:e55387. doi: 10.1371/journal.pone.0055387.
    1. Kirchner S., Kieu T., Chow C., Casey S., Blumberg B. Prenatal exposure to the environmental obesogen tributyltin predisposes multipotent stem cells to become adipocytes. Mol. Endocrinol. 2010;24:526–539. doi: 10.1210/me.2009-0261.
    1. Skinner M.K., Manikkam M., Tracey R., Guerrero-Bosagna C., Haque M., Nilsson E.E. Ancestral dichlorodiphenyltrichloroethane (DDT) exposure promotes epigenetic transgenerational inheritance of obesity. BMC Med. 2013;11:228. doi: 10.1186/1741-7015-11-228.
    1. Ma Y., Xia W., Wang D.Q., Wan Y.J., Xu B., Chen X., Li Y.Y., Xu S.Q. Hepatic DNA methylation modifications in early development of rats resulting from perinatal BPA exposure contribute to insulin resistance in adulthood. Diabetologia. 2013;56:2059–2067. doi: 10.1007/s00125-013-2944-7.
    1. Le Magueresse-Battistoni B., Labaronne E., Vidal H., Naville D. Endocrine disrupting chemicals in mixture and obesity, diabetes and related metabolic disorders. World J. Biol. Chem. 2017;8:108–119. doi: 10.4331/wjbc.v8.i2.108.
    1. Michalek J.E., Pavuk M. Diabetes and cancer in veterans of Operation Ranch Hand after adjustment for calendar period, days of spraying, and time spent in Southeast Asia. J. Occup. Environ. Med. 2008;50:330–340. doi: 10.1097/JOM.0b013e31815f889b.
    1. Pesatori A.C., Consonni D., Bachetti S., Zocchetti C., Bonzini M., Baccarelli A., Bertazzi P.A. Short- and long-term morbidity and mortality in the population exposed to dioxin after the “Seveso accident”. Ind. Health. 2003;41:127–138. doi: 10.2486/indhealth.41.127.
    1. Mustieles V., Fernández M.F., Martin-Olmedo P., González-Alzaga B., Fontalba-Navas A., Hauser R., Olea N., Arrebola J.P. Human adipose tissue levels of persistent organic pollutants and metabolic syndrome components: Combining a cross-sectional with a 10-year longitudinal study using a multi-pollutant approach. Environ. Int. 2017;104:48–57. doi: 10.1016/j.envint.2017.04.002.
    1. Gauthier M.S., Rabasa-Lhoret R., Prud’homme D., Karelis A.D., Geng D., van Bavel B., Ruzzin J. The metabolically healthy but obese phenotype is associated with lower plasma levels of persistent organic pollutants as compared to the metabolically abnormal obese phenotype. J. Clin. Endocrinol. Metab. 2014;99:E1061–E1066. doi: 10.1210/jc.2013-3935.
    1. Wang T., Li M., Chen B., Xu M., Xu Y., Huang Y., Lu J., Chen Y., Wang W., Li X., et al. Urinary bisphenol A (BPA) concentration associates with obesity and insulin resistance. J. Clin. Endocrinol. Metab. 2012;97:E223–E227. doi: 10.1210/jc.2011-1989.
    1. Carwile J.L., Michels K.B. Urinary bisphenol A and obesity: NHANES 2003–2006. Environ. Res. 2011;111:825–830. doi: 10.1016/j.envres.2011.05.014.
    1. Hatch E.E., Nelson J.W., Qureshi M.M., Weinberg J., Moore L.L., Singer M., Webster T.F. Association of urinary phthalate metabolite concentrations with body mass index and waist circumference: A cross-sectional study of NHANES data, 1999–2002. Environ. Health. 2008;7:27. doi: 10.1186/1476-069X-7-27.
    1. Stahlhut R.W., van Wijngaarden E., Dye T.D., Cook S., Swan S.H. Concentrations of urinary phthalate metabolites are associated with increased waist circumference and insulin resistance in adult U.S. males. Environ. Health Perspect. 2007;115:876–882. doi: 10.1289/ehp.9882.
    1. Smerieri A., Testa C., Lazzeroni P., Nuti F., Grossi E., Cesari S., Montanini L., Latini G., Bernasconi S., Papini A.M., et al. Di-(2-ethylhexyl) phthalate metabolites in urine show age-related changes and associations with adiposity and parameters of insulin sensitivity in childhood. PLoS ONE. 2015;10:e0117831. doi: 10.1371/journal.pone.0117831.
    1. Bergman A., Heindel J.J., Jobling S. WHO/UNEP; 2013. [(accessed on 15 February 2018)]. State of the Science of Endocrine Disrupting Chemicals—2012. Available online: .
    1. Arbuckle T.E., Davis K., Marro L., Fisher M., Legrand M., LeBlanc A., Gaudreau E., Foster W.G., Choeurng V., Fraser W.D., et al. Phthalate and bisphenol A exposure among pregnant women in Canada—Results from the MIREC study. Environ. Int. 2014;68:55–65. doi: 10.1016/j.envint.2014.02.010.
    1. Woodruff T.J., Zota A.R., Schwartz J.M. Environmental chemicals in pregnant women in the United States: NHANES 2003–2004. Environ. Health Perspect. 2011;119:878–885. doi: 10.1289/ehp.1002727.
    1. Lenters V., Portengen L., Rignell-Hydbom A., Jönsson B.A., Lindh C.H., Piersma A.H., Toft G., Bonde J.P., Heederik D., Rylander L., Vermeulen R. Prenatal phthalate, perfluoroalkyl acid, and organochlorine exposures and term birth weight in three birth cohorts: Multi-pollutant models based on elastic net regression. Environ. Health Perspect. 2016;124:365–372. doi: 10.1289/ehp.1408933.
    1. Birks L., Casas M., Garcia A.M., Alexander J., Barros H., Bergström A., Bonde J.P., Burdorf A., Costet N., Danileviciute A., et al. Occupational exposure to endocrine-disrupting chemicals and birth weight and length of gestation: A European meta-analysis. Environ. Health Perspect. 2016;124:1785–1793. doi: 10.1289/EHP208.
    1. Govarts E., Nieuwenhuijsen M., Schoeters G., Ballester F., Bloemen K., de Boer M., Chevrier C., Eggesbø M., Guxens M., Krämer U., et al. Birth weight and prenatal exposure to polychlorinated biphenyls (PCBs) and dichlorodiphenyldichloroethylene (DDE): A meta-analysis within 12 European birth cohorts. Environ. Health Perspect. 2012;120:162–170. doi: 10.1289/ehp.1103767.
    1. Philippat C., Mortamais M., Chevrier C., Petit C., Calafat A.M., Ye X., Silva M.J., Brambilla C., Pin I., Charles M.A., et al. Exposure to phthalates and phenols during pregnancy and offspring size at birth. Environ. Health Perspect. 2012;120:464–470. doi: 10.1289/ehp.1103634.
    1. Zhang Y., Lin L., Cao Y., Chen B., Zheng L., Ge R.S. Phthalate levels and low birth weight: A nested case-control study of Chinese newborns. J. Pediatr. 2009;155:500–504. doi: 10.1016/j.jpeds.2009.04.007.
    1. Wolff M.S., Engel S.M., Berkowitz G.S., Ye X., Silva M.J., Zhu C., Wetmur J., Calafat A.M. Prenatal phenol and phthalate exposures and birth outcomes. Environ. Health Perspect. 2008;116:1092–1097. doi: 10.1289/ehp.11007.
    1. Serme-Gbedo Y.K., Abdelouahab N., Pasquier J.C., Cohen A.A., Takser L. Maternal levels of endocrine disruptors, polybrominated diphenyl ethers, in early pregnancy are not associated with lower birth weight in the Canadian birth cohort GESTE. Environ. Health. 2016;15:49. doi: 10.1186/s12940-016-0134-z.
    1. Lignell S., Aune M., Darnerud P.O., Hanberg A., Larsson S.C., Glynn A. Prenatal exposure to polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) may influence birth weight among infants in a Swedish cohort with background exposure: A cross-sectional study. Environ. Health. 2013;12:44. doi: 10.1186/1476-069X-12-44.
    1. Alaee M., Arias P., Sjödin A., Bergman A. An overview of commercially used brominated flame retardants, their applications, their use patterns in different countries/regions and possible modes of release. Environ. Int. 2003;29:683–689. doi: 10.1016/S0160-4120(03)00121-1.
    1. Sferruzzi-Perri A.N., Vaughan O.R., Forhead A.J., Fowden A.L. Hormonal and nutritional drivers of intrauterine growth. Curr. Opin. Clin. Nutr. Metab. Care. 2013;16:298–309. doi: 10.1097/MCO.0b013e32835e3643.
    1. Ceccatelli R., Faass O., Schlumpf M., Lichtensteiger W. Gene expression and estrogen sensitivity in rat uterus after developmental exposure to the polybrominated diphenylether PBDE 99 and PCB. Toxicology. 2006;220:104–116. doi: 10.1016/j.tox.2005.12.004.
    1. Shy C.G., Huang H.L., Chao H.R., Chang-Chien G.P. Cord blood levels of thyroid hormones and IGF-1 weakly correlate with breast milk levels of PBDEs in Taiwan. Int. J. Hyg. Environ. Health. 2012;215:345–351. doi: 10.1016/j.ijheh.2011.10.004.
    1. Xu X., Yekeen T.A., Xiao Q., Wang Y., Lu F., Huo X. Placental IGF-1 and IGFBP-3 expression correlate with umbilical cord blood PAH and PBDE levels from prenatal exposure to electronic waste. Environ. Pollut. 2013;182:63–69. doi: 10.1016/j.envpol.2013.07.005.
    1. Lopez-Espinosa M.J., Costa O., Vizcaino E., Murcia M., Fernandez-Somoano A., Iñiguez C. Prenatal Exposure to Polybrominated Flame Retardants and Fetal Growth in the INMA Cohort (Spain) Environ. Sci. Technol. 2015;49:10108–10116. doi: 10.1021/acs.est.5b01793.
    1. Foster W.G., Gregorovich S., Morrison K.M., Atkinson S.A., Kubwabo C., Stewart B. Human maternal and umbilical cord blood concentrations of polybrominated diphenyl ethers. Chemosphere. 2011;84:1301–1309. doi: 10.1016/j.chemosphere.2011.05.028.
    1. Harley K.G., Chevrier J., Aguilar Schall R., Sjödin A., Bradman A., Eskenazi B. Association of prenatal exposure to polybrominated diphenyl ethers and infant birth weight. Am. J. Epidemiol. 2011;174:885–892. doi: 10.1093/aje/kwr212.
    1. Chao H.R., Wang S.L., Lee W.J., Wang Y.F., Päpke O. Levels of polybrominated diphenyl ethers (PBDEs) in breast milk from central Taiwan and their relation to infant birth outcome and maternal menstruation effects. Environ. Int. 2007;33:239–245. doi: 10.1016/j.envint.2006.09.013.
    1. Chen L., Wang C., Cui C., Ding G., Zhou Y., Jin J., Gao Y., Tian Y. Prenatal exposure to polybrominated diphenyl ethers and birth outcomes. Environ. Pollut. 2015;206:32–37. doi: 10.1016/j.envpol.2015.06.019.
    1. Xu X.H., Zhang J., Wang Y.M., Ye Y.P., Luo Q.Q. Perinatal exposure to bisphenol-A impairs learning-memory by concomitant down-regulation of N-methyl-d-aspartate receptors of hippocampus in male offspring mice. Horm. Behav. 2010;58:326–333. doi: 10.1016/j.yhbeh.2010.02.012.
    1. Chou W.C., Chen J.L., Lin C.F., Chen Y.C., Shih F.C., Chuang C.Y. Biomonitoring of bisphenol A concentrations in maternal and umbilical cord blood in regard to birth outcomes and adipokine expression: A birth cohort study in Taiwan. Environ. Health. 2011;10:94. doi: 10.1186/1476-069X-10-94.
    1. Veiga-Lopez A., Kannan K., Liao C., Ye W., Domino S.E., Padmanabhan V. Gender-Specific Effects on Gestational Length and Birth Weight by Early Pregnancy BPA Exposure. J. Clin. Endocrinol. Metab. 2015;100:E1394–E1403. doi: 10.1210/jc.2015-1724.
    1. Lee Y.M., Hong Y.C., Ha M., Kim Y., Park H., Kim H.S., Ha E.H. Prenatal Bisphenol-A exposure affects fetal length growth by maternal glutathione transferase polymorphisms, and neonatal exposure affects child volume growth by sex: From multiregional prospective birth cohort MOCEH study. Sci. Total Environ. 2018;612:1433–1441. doi: 10.1016/j.scitotenv.2017.08.317.
    1. Bach C.C., Bech B.H., Brix N., Nohr E.A., Bonde J.P., Henriksen T.B. Perfluoroalkyl and polyfluoroalkyl substances and human fetal growth: A systematic review. Crit. Rev. Toxicol. 2015;45:53–67. doi: 10.3109/10408444.2014.952400.
    1. Manzano-Salgadoa C.B., Casasa M., Lopez-Espinosa M.J., Ballester F., Iñiguez C., Martineza D., Costad O., Santa-Marina L., Pereda-Pereda E., Schettgenh T., et al. Prenatal exposure to perfluoroalkyl substances and birth outcomes in a Spanish birth cohort. Environ. Int. 2017;108:278–284. doi: 10.1016/j.envint.2017.09.006.
    1. Lauritzen H.B., Larose T.L., Øien T., Sandanger T.M., Odland J.O., van de Bor M., Jacobsen G.W. Maternal serum levels of perfluoroalkyl substances and organochlorines and indices of fetal growth: A Scandinavian case–cohort study. Pediatr. Res. 2017;81:33–42. doi: 10.1038/pr.2016.187.
    1. Gore A.C., Chappell V.A., Fenton S.E., Flaws J.A., Nadal A., Prins G.S., Toppari J., Zoeller R.T. EDC-2: The Endocrine Society’s second scientific statement on Endocrine-Disrupting Chemicals. Endocr. Rev. 2015;36:E1–E150. doi: 10.1210/er.2015-1010.
    1. Hartoft-Nielsen M.L., Boas M., Bliddal S., Rasmussen A.K., Main K., Feldt-Rasmussen U. Do thyroid disrupting chemicals influence foetal development during pregnancy? J. Thyr. Res. 2011;2011:1–14. doi: 10.4061/2011/342189.
    1. Preau L., Fini J.B., Morvan-Dubois G., Demeneix B. Thyroid hormone signaling during early neurogenesis and its significance as a vulnerable window for endocrine disruption. Biochim. Biophys. Acta. 2015;1849:112–121. doi: 10.1016/j.bbagrm.2014.06.015.
    1. Gilbert M.E., Rovet J., Chen Z., Koibuchi N. Developmental thyroid hormone disruption: Prevalence, environmental contaminants and neurodevelopmental consequences. Neurotoxicology. 2012;33:842–852. doi: 10.1016/j.neuro.2011.11.005.
    1. Blount B.C., Pirkle J.L., Osterloh J.D., Valentin-Blasini L., Caldwell K.L. Urinary perchlorate and thyroid hormone levels in adolescent and adult men and women living in the United States. Environ Health Perspect. 2006;114:1865–1871. doi: 10.1289/ehp.9466.
    1. Steinmaus C., Miller M.D., Howd R. Impact of smoking and thiocyanate on perchlorate and thyroid hormone associations in the 2001–2002 National Health and Nutrition Examinatio Survey. Environ. Health Perspect. 2007;115:1333–1338. doi: 10.1289/ehp.10300.
    1. Wu M.T., Wu C.F., Chen B.H., Chen E.K., Chen Y.L., Shiea J., Lee W.T., Chao M.C., Wu J.R. Intake of phthalate-tainted foods alters thyroid functions in Taiwanese children. PLoS ONE. 2013;8:e55005. doi: 10.1371/journal.pone.0055005.
    1. El Majidi N., Bouchard M., Carrier G. Systematic analysis of the relationship between standardized biological levels of polychlorinated biphenyls and thyroid function in pregnant women and newborns. Chemosphere. 2014;98:1–17. doi: 10.1016/j.chemosphere.2013.10.006.
    1. Gentilcore D., Porreca I., Rizzo F., Ganbaatar E., Carchia E., Mallardo M., De Felice M., Ambrosino C. Bisphenol A interferes with thyroid specific gene expression. Toxicology. 2013;304:21–31. doi: 10.1016/j.tox.2012.12.001.
    1. Kuriyama S.N., Wanner A., Fidalgo-Neto A.A., Talsness C.E., Koerner W., Chahoud I. Developmental exposure to low-dose PBDE-99: Tissue distribution and thyroid hormone levels. Toxicology. 2007;242:80–90. doi: 10.1016/j.tox.2007.09.011.
    1. Ibhazehiebo K., Koibuchi N. Thyroid hormone receptor-mediated transcription is suppressed by low dose phthalate. Niger. J. Physiol. Sci. 2011;26:143–149.
    1. Giera S., Bansal R., Ortiz-Toro T.M., Taub D.G., Zoeller R.T. Individual polychlorinated biphenyl (PCB) congeners produce tissue- and gene-specific effects on thyroid hormone signaling during development. Endocrinology. 2011;152:2909–2919. doi: 10.1210/en.2010-1490.
    1. Hallgren S., Sinjari T., Håkansson H., Darnerud P.O. Effects of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) on thyroid hormone and vitamin A levels in rats and mice. Arch. Toxicol. 2001;75:200–208. doi: 10.1007/s002040000208.
    1. O’Connor J.C., Frame S.R., Ladics G.S. Evaluation of a 15-day screening assay using intact male rats for identifying antiandrogens. Toxicol. Sci. 2002;69:92–108. doi: 10.1093/toxsci/69.1.92.
    1. Chevrier J., Warner M., Gunier R.B., Brambilla P., Eskenazi B., Mocarelli P. Serum Dioxin Concentrations and Thyroid Hormone Levels in the Seveso Women’s Health Study. Am. J. Epidemiol. 2014;180:490–498. doi: 10.1093/aje/kwu160.
    1. Shimizu R., Yamaguchi M., Uramaru N., Kuroki H., Ohta S., Kitamura S., Sugihara K. Structure-activity relationships of 44 halogenated compounds for iodotyrosine deiodinase-inhibitory activity. Toxicology. 2013;314:22–29. doi: 10.1016/j.tox.2013.08.017.
    1. Moriyama K., Tagami T., Akamizu T., Usui T., Saijo M., Kanamoto N., Hataya Y., Shimatsu A., Kuzuya H., Nakao K. Thyroid hormone action is disrupted by bisphenol A as an antagonist. J. Clin. Endocrinol. Metab. 2002;87:5185–5190. doi: 10.1210/jc.2002-020209.
    1. Zoeller R.T., Dowling A.L., Vas A.A. Developmental exposure to polychlorinated biphenyls exerts thyroid hormone-like effects on the expression of RC3/neurogranin and myelin basic protein messenger ribonucleic acids in the developing rat brain. Endocrinology. 2000;141:181–189. doi: 10.1210/endo.141.1.7273.
    1. Londoño M., Shimokawa N., Miyazaki W., Iwasaki T., Koibuchi N. Hydroxylated PCB induces Ca2+ oscillations and alterations of membrane potential in cultured cortical cells. J. Appl. Toxicol. 2010;30:334–342. doi: 10.1002/jat.1501.
    1. Bansal R., Tighe D., Danai A., Rawn D.F., Gaertner D.W., Arnold D.L., Gilbert M.E., Zoeller R.T. Polybrominated diphenyl ether (DE-71) interferes with thyroid hormone action independent of effects on circulating levels of thyroid hormone in male rats. Endocrinology. 2014;155:4104–4112. doi: 10.1210/en.2014-1154.
    1. Schmutzler C., Gotthardt I., Hofmann P.J., Radovic B., Kovacs G., Stemmler L., Nobis I., Bacinski A., Mentrup B., Ambrugger P., et al. Endocrine Disruptors and the thyroid gland—A combined in vitro and in vivo analysis of potential new biomarkers. Environ. Health Perspect. 2007;115:77–83. doi: 10.1289/ehp.9369.
    1. Charatcharoenwitthaya N., Ongphiphadhanakul B., Pearce E.N., Somprasit C., Chanthasenanont A., He X., Chailurkit L., Braverman L.E. The association between perchlorate and thiocyanate exposure and thyroid function in first-trimester pregnant Thai women. J. Clin. Endocrinol. Metab. 2014;99:2365–2371. doi: 10.1210/jc.2013-3986.
    1. Taylor P.N., Okosieme O.E., Murphy R., Hales C., Chiusano E., Maina A., Joomun M., Bestwick J.P., Smyth P., Paradice R., et al. Maternal perchlorate levels in women with borderline thyroid function during pregnancy and the cognitive development of their offspring: Data from the controlled antenatal thyroid study. J. Clin. Endocrinol. Metab. 2014;99:4291–4298. doi: 10.1210/jc.2014-1901.
    1. Schantz S.L., Widholm J.J., Rice D.C. Effects of PCB exposure on neuropsychological function in children. Environ. Health Perspect. 2003;111:357–376. doi: 10.1289/ehp.5461.
    1. Zoeller R.T., Dowling A.L.S., Herzig C.T.A., Iannacone E.A., Gauger K.J., Bansal R. Thyroid hormone, brain development, and the environment. Environ. Health Perspect. 2002;110:355–361. doi: 10.1289/ehp.02110s3355.
    1. Jacobson J.L., Jacobson S.W. Intellectual impairment in children exposed to polychlorinated biphenyls in utero. N. Engl. J. Med. 1996;335:783–789. doi: 10.1056/NEJM199609123351104.
    1. Parent A.S., Franssen D., Fudvoye J., Gerard A., Bourguignon J.P. Developmental variations in environmental influences including endocrine disruptors on pubertal timing and neuroendocrine control: Revision of human observations and mechanistic insight from rodents. Front. Neuroendocrinol. 2015;38:12–36. doi: 10.1016/j.yfrne.2014.12.004.
    1. Aksglaede L., Sorensen K., Petersen J.H., Skakkebaek N.E., Juul A. Recent decline in age at breast development: The Copenhagen Puberty Study. Pediatrics. 2009;123:e932–e939. doi: 10.1542/peds.2008-2491.
    1. Herman-Giddens M.E., Slora E.J., Wasserman R.C., Bourdony C.J., Bhapkar M.V., Koch G.G., Hasemeier C.M. Secondary sexual characteristics and menses in young girls seen in office practice: A study from the Pediatric Research in Office Settings network. Pediatrics. 1997;99:505–512. doi: 10.1542/peds.99.4.505.
    1. Liwnicz B.H., Liwnicz R.G. On endocrine function. In: Kaplan L.A., Pesce A.J., editors. Clinical Chemistry: Theory, Analysis and Correlation. 2nd ed. CV Mosby Company; St. Lewis, MO, USA: 1989. pp. 607–619.
    1. Buck Louis G.M., Gray L.E., Jr., Marcus M., Ojeda S.R., Pescovitz O.H., Witchel S.F., Sippell W., Abbott D.H., Soto A., Tyl R.W., et al. Environmental factors and puberty timing: Expert panel research needs. Pediatrics. 2008;121:S192–S207. doi: 10.1542/peds.1813E.
    1. Bourguignon J.P., Juul A., Franssen D., Fudvoye J., Pinson A., Parent A.S. Contribution of the endocrine perspective in the evaluation of endocrine disrupting chemical effects: The case study of pubertal timing. Horm. Res. Paediatr. 2016;86:221–232. doi: 10.1159/000442748.
    1. Scippo M.L., Argiris C., Van De Weerdt C., Muller M., Willemsen P., Martial J., Maghuin-Rogister G. Recombinant human estrogen, androgen and progesterone receptors for detection of potential endocrine disruptors. Anal. Bioanal. Chem. 2004;378:664–669. doi: 10.1007/s00216-003-2251-0.
    1. Caserta D., Maranghi L., Mantovani A., Marci R., Maranghi F., Moscarini M. Impact of endocrine disruptor chemicals in gynaecology. Hum. Reprod. Update. 2008;14:59–72. doi: 10.1093/humupd/dmm025.
    1. Rasier G., Toppari J., Parent A.S., Bourguignon J.P. Female sexual maturation and reproduction after prepubertal exposure to estrogens and endocrine disrupting chemicals: A review of rodent and human data. Mol. Cell. Endocrinol. 2006;254–255:187–201. doi: 10.1016/j.mce.2006.04.002.
    1. Diamanti-Kandarakis E., Bourguignon J.P., Giudice L.C., Hauser R., Prins G.S., Soto A.M., Zoeller R.T., Gore A.C. Endocrine-disrupting chemicals: An Endocrine Society scientific statement. Endocr. Rev. 2009;30:293–342. doi: 10.1210/er.2009-0002.
    1. Krstevska-Konstantinova M., Charlier C., Craen M., Du Caju M., Heinrichs C., de Beaufort C., Plomteux G., Bourguignon J.P. Sexual precocity after immigration from developing countries to Belgium: Evidence of previous exposure to organochlorine pesticides. Hum. Reprod. 2001;16:1020–1026. doi: 10.1093/humrep/16.5.1020.
    1. Parent A.S., Teilmann G., Juul A., Skakkebaek N.E., Toppari J., Bourguignon J.P. The timing of normal puberty and the age limits of sexual precocity: Variations around the world, secular trends, and changes after migration. Endocr. Rev. 2001;24:668–693. doi: 10.1210/er.2002-0019.
    1. Vasiliu O., Muttineni J., Karmaus W. In utero exposure to organochlorines and age at menarche. Hum. Reprod. 2004;19:1506–1512. doi: 10.1093/humrep/deh292.
    1. Gladen B.C., Ragan N.B., Rogan W.J. Pubertal growth and development and prenatal and lactational exposure to polychlorinated biphenyls and dichlorodiphenyl dichloroethene. J. Pediatr. 2000;136:490–496. doi: 10.1016/S0022-3476(00)90012-X.
    1. Ouyang F., Perry M.J., Venners S.A., Chen C., Wang B., Yang F., Fang Z., Zang T., Wang L., Xu X., et al. Serum DDT, age at menarche, and abnormal menstrual cycle length. Occup. Environ. Med. 2005;62:878–884. doi: 10.1136/oem.2005.020248.
    1. Chen A., Chung E., DeFranco E.A., Pinney S.M., Dietrich K.N. Serum PBDEs and age at menarche in adolescent girls: Analysis of the National Health and Nutrition Examination Survey 2003–2004. Environ. Res. 2011;111:831–837. doi: 10.1016/j.envres.2011.05.016.
    1. Tassinari R., Mancini F.R., Mantovani A., Busani L., Maranghi F. Pilot study on the dietary habits and lifestyles of girls with idiopathic precocious puberty from the city of Rome: Potential impact of exposure to flame retardant polybrominated diphenyl ethers. J. Pediatr. Endocrinol. Metab. 2015;28:1369–1372. doi: 10.1515/jpem-2015-0116.
    1. Link B., Gabrio T., Mann V., Schilling B., Maisner V., König M., Flicker-Klein A., Zöllner I., Fischer G. Polybrominated diphenyl ethers (PBDE) in blood of children in Baden-Württemberg between 2002/03 and 2008/09. Int. J. Hyg. Environ. Health. 2012;215:224–228. doi: 10.1016/j.ijheh.2011.10.018.
    1. Deodati A., Sallemi A., Maranghi F., Germani D., Puglianiello A., Baldari F., Busani L., Mancini F.R., Tassinari R., Mantovani A., et al. Serum levels of polybrominated diphenyl ethers in girls with premature thelarche. Horm. Res. Paediatr. 2016;86:233–239. doi: 10.1159/000444586.
    1. Blanck H.M., Marcus M., Tolbert P.E., Rubin C., Henderson A.K., Hertzberg V.S., Zhang R.H., Cameron L. Age at menarche and tanner stage in girls exposed in utero and postnatally to polybrominated biphenyl. Epidemiology. 2000;11:641–647. doi: 10.1097/00001648-200011000-00005.
    1. Harley K.G., Rauch S.A., Chevrier J., Kogut K., Parra K.L., Trujillo C., Lustig R.H., Greenspan L.C., Sjödin A., Bradman A., et al. Association of prenatal and childhood PBDE exposure with timing of puberty in boys and girls. Environ. Int. 2017;100:132–138. doi: 10.1016/j.envint.2017.01.003.
    1. Wormke M., Stoner M., Saville B., Walker K., Abdelrahim M., Burghardt R., Safe S. The aryl hydrocarbon receptor mediates degradation of estrogen receptor alpha through activation of proteasomes. Mol. Cell. Biol. 2003;23:1843–1855. doi: 10.1128/MCB.23.6.1843-1855.2003.
    1. Leijs M.M., Koppe J.G., Olie K., van Aalderen W.M., Voogt P., Vulsma T., Westra M., ten Tusscher G.W. Delayed initiation of breast development in girls with higher prenatal dioxin exposure: A longitudinal cohort study. Chemosphere. 2008;73:999–1004. doi: 10.1016/j.chemosphere.2008.05.053.
    1. Den Hond E., Roels H.A., Hoppenbrouwers K., Nawrot T., Thijs L., Vandermeulen C., Winneke G., Vanderschueren D., Staessen J.A. Sexual maturation in relation to polychlorinated aromatic hydrocarbons: Sharpe and Skakkebaek’s hypothesis revisited. Environ. Health Perspect. 2002;110:771–776. doi: 10.1289/ehp.02110771.
    1. Warner M., Samuels S., Mocarelli P., Gerthoux P.M., Needham L., Patterson D.G., Jr., Eskenazi B. Serum dioxin concentrations and age at menarche. Environ. Health Perspect. 2004;112:1289–1292. doi: 10.1289/ehp.7004.
    1. Bongiovanni A.M. An epidemic of premature thelarche in Puerto Rico. J. Pediatr. 1983;103:245–246. doi: 10.1016/S0022-3476(83)80354-0.
    1. Bourdony C.J. Premature Thelarche and Early Sexual Development Registry. Annual Report; Department of Health; San Juan, Puerto Rico: 1998.
    1. Colon I., Caro D., Bourdony C.J., Rosario O. Identification of phthalate esters in the serum of young Puerto Rican girls with premature breast development. Environ. Health Perspect. 2000;108:895–900. doi: 10.1289/ehp.00108895.
    1. Frederiksen H., Sorensen K., Mouritsen A., Aksglaede L., Hagen C.P., Petersen J.H., Skakkebaek N.E., Andersson A.M., Juul A. High urinary phthalate concentration associated with delayed pubarche in girls. Int. J. Androl. 2012;35:216–226. doi: 10.1111/j.1365-2605.2012.01260.x.
    1. Mouritsen A., Frederiksen H., Sorensen K., Aksglaede L., Hagen C., Skakkebaek N.E., Main K.M., Andersson A.M., Juul A. Urinary phthalates from 168 girls and boys measured twice a year during a 5-year period: Associations with adrenal androgen levels and puberty. J. Clin. Endocrinol. Metab. 2013;98:3755–3764. doi: 10.1210/jc.2013-1284.
    1. Srilanchakon K., Thadsri T., Jantarat C., Thengyai S., Nosoognoen W., Supornsilchai V. Higher phthalate concentrations are associated with precocious puberty in normal weight Thai girls. J. Pediatr. Endocrinol. Metab. 2017;30:1293–1298. doi: 10.1515/jpem-2017-0281.
    1. Buluş A.D., Aşci A., Erkekoglu P., Balci A., Andiran N., Koçer-Gümüşel B. The evaluation of possible role of endocrine disruptors in central and peripheral precocious puberty. Toxicol. Mech. Methods. 2016;26:493–500. doi: 10.3109/15376516.2016.1158894.
    1. Wolff M.S., Pajak A., Pinney S.M., Windham G.C., Galvez M., Rybak M., Silva M.J., Ye X., Calafat A.M., Kushi L.H., et al. Associations of urinary phthalate and phenol biomarkers with menarche in a multiethnic cohort of young girls. Reprod. Toxicol. 2017;67:56–64. doi: 10.1016/j.reprotox.2016.11.009.
    1. Leonardi A., Cofini M., Rigante D., Lucchetti L., Cipolla C., Penta L., Esposito S. The effect of bisphenol A on puberty: A critical review of the medical literature. Int. J. Environ. Res. Public Health. 2017;14:1044. doi: 10.3390/ijerph14091044.
    1. Supornsilchai V., Jantarat C., Nosoognoen W., Pornkunwilai S., Wacharasindhu S., Soder O. Increased levels of bisphenol A (BPA) in Thai girls with precocious puberty. J. Pediatr. Endocrinol. Metab. 2016;29:1233–1239. doi: 10.1515/jpem-2015-0326.
    1. Durmaz E., Aşçı A., Erkekoğlu P., Akçurin S., Gümüşel B.K., Bircan I. Urinary bisphenol a levels in girls with idiopathic central precocious puberty. J. Clin. Res. Pediatr. Endocrinol. 2014;6:16–21. doi: 10.4274/Jcrpe.1220.
    1. McGuinn L.A., Ghazarian A.A., Joseph Su L., Ellison G.L. Urinary bisphenol A and age at menarche among adolescent girls: Evidence from NHANES 2003–2010. Environ. Res. 2015;136:381–386. doi: 10.1016/j.envres.2014.10.037.
    1. Miao M., Wang Z., Liu X., Liang H., Zhou Z., Tan H., Yuan W., Li D.K. Urinary bisphenol A and pubertal development in Chinese school-aged girls: A cross-sectional study. Environ. Health. 2017;16:80. doi: 10.1186/s12940-017-0290-9.
    1. Wolff M.S., Teitelbaum S.L., Pinney S.M., Windham G., Liao L., Biro F., Kushi L.H., Erdmann C., Hiatt R.A., Rybak M.E., et al. Investigation of relationships between urinary biomarkers of phytoestrogens, phthalates and phenols and pubertal stages in girls. Environ. Health Perspect. 2010;118:1039–1046. doi: 10.1289/ehp.0901690.
    1. Virtanen H.E., Jørgensen N., Toppari J. Semen quality in the 21st century. Nat. Rev. Urol. 2017;14:120–130. doi: 10.1038/nrurol.2016.261.
    1. Centola G.M., Blanchard A., Demick J., Li S., Eisenberg M.L. Decline in sperm count and motility in young adult men from 2003 to 2013: Observations from a U.S. sperm bank. Andrology. 2016;4:270–276. doi: 10.1111/andr.12149.
    1. Carlsen E., Giwercman A., Keiding N., Skakkebaek N.E. Evidence for decreasing quality of semen during past 50 years. BMJ. 1992;305:609–613. doi: 10.1136/bmj.305.6854.609.
    1. Nordkap L., Joensen U.N., Blomberg J.M., Jørgensen N. Regional differences and temporal trends in male reproductive health disorders: Semen quality may be a sensitive marker of environmental exposures. Mol. Cell. Endocrinol. 2012;355:221–230. doi: 10.1016/j.mce.2011.05.048.
    1. Sifakis S., Androutsopoulos V.P., Tsatsakis A.M., Spandidos D.A. Human exposure to endocrine disrupting chemicals: Effects on the male and female reproductive systems. Environ. Toxicol. Pharmacol. 2017;51:56–70. doi: 10.1016/j.etap.2017.02.024.
    1. Patiño-García D., Cruz-Fernandes L., Buñay J., Palomino J., Moreno R.D. Reproductive Alterations in Chronically Exposed Female Mice to Environmentally Relevant Doses of a Mixture of Phthalates and Alkylphenols. Endocrinology. 2018;159:1050–1061. doi: 10.1210/en.2017-00614.
    1. Zhou C., Gao L., Flaws J.A. Prenatal exposure to an environmentally relevant phthalate mixture disrupts reproduction in F1 female mice. Toxicol. Appl. Pharmacol. 2017;318:49–57. doi: 10.1016/j.taap.2017.01.010.
    1. Latchney S.E., Fields A.M., Susiarjo M. Linking inter-individual variability to endocrine disruptors: Insights for epigenetic inheritance. Mamm. Genome. 2018;29:141–152. doi: 10.1007/s00335-017-9729-0.
    1. Durmaz E., Asci A., Erkekoglu P., Balcı A., Bircan I., Koçer-Gumusel B. Urinary bisphenol A levels in Turkish girls with premature thelarche. Hum. Exp. Toxicol. 2018;1:960327118756720. doi: 10.1177/0960327118756720.
    1. Watkins D.J., Sánchez B.N., Téllez-Rojo M.M., Lee J.M., Mercado-García A., Blank-Goldenberg C., Peterson K.E., Meeker J.D. Phthalate and bisphenol A exposure during in utero windows of susceptibility in relation to reproductive hormones and pubertal development in girls. Environ. Res. 2017;159:143–151. doi: 10.1016/j.envres.2017.07.051.
    1. Zhou W., Fang F., Zhu W., Chen Z.J., Du Y., Zhang J. Bisphenol A and Ovarian Reserve among Infertile Women with Polycystic Ovarian Syndrome. Int. J. Environ. Res. Public Health. 2016;14:18. doi: 10.3390/ijerph14010018.
    1. Mínguez-Alarcón L., Gaskins A.J., Chiu Y.H., Williams P.L., Ehrlich S., Chavarro J.E., Petrozza J.C., Ford J.B., Calafat A.M., Hauser R., et al. Urinary bisphenol A concentrations and association with in vitro fertilization outcomes among women from a fertility clinic. Hum. Reprod. 2015;30:2120–2128. doi: 10.1093/humrep/dev183.
    1. Upson K., Sathyanarayana S., De Roos A.J., Koch H.M., Scholes D., Holt V.L. A population-based case-control study of urinary bisphenol A concentrations and risk of endometriosis. Hum. Reprod. 2014;29:2457–2464. doi: 10.1093/humrep/deu227.
    1. Jukic A.M., Calafat A.M., McConnaughey D.R., Longnecker M.P., Hoppin J.A., Weinberg C.R., Wilcox A.J., Baird D.D. Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss. Environ. Health Perspect. 2016;124:321–328. doi: 10.1289/ehp.1408164.
    1. Thomsen A.M., Riis A.H., Olsen J., Jönsson B.A., Lindh C.H., Hjollund N.H., Jensen T.K., Bonde J.P., Toft G. Female exposure to phthalates and time to pregnancy: A first pregnancy planner study. Hum. Reprod. 2017;32:232–238. doi: 10.1093/humrep/dew291.
    1. Mu D., Gao F., Fan Z., Shen H., Peng H., Hu J. Levels of Phthalate Metabolites in Urine of Pregnant Women and Risk of Clinical Pregnancy Loss. Environ. Sci. Technol. 2015;49:10651–10657. doi: 10.1021/acs.est.5b02617.
    1. Al-Hussaini T.K., Abdelaleem A.A., Elnashar I., Shabaan O.M., Mostafa R., El-Baz M.A.H., El-Deek S.E.M., Farghaly T.A. The effect of follicullar fluid pesticides and polychlorinated biphenyls concentrations on intracytoplasmic sperm injection (ICSI) embryological and clinical outcome. Eur. J. Obstet. Gynecol. Reprod. Biol. 2018;220:39–43. doi: 10.1016/j.ejogrb.2017.11.003.
    1. Ploteau S., Cano-Sancho G., Volteau C., Legrand A., Vénisseau A., Vacher V., Marchand P., Le Bizec B., Antignac J.P. Associations between internal exposure levels of persistent organic pollutants in adipose tissue and deep infiltrating endometriosis with or without concurrent ovarian endometrioma. Environ. Int. 2017;108:195–203. doi: 10.1016/j.envint.2017.08.019.
    1. Hart R.J., Doherty D.A., Keelan J.A., Minaee N.S., Thorstensen E.B., Dickinson J.E., Pennell C.E., Newnham J.P., McLachlan R., Norman R.J., et al. The impact of antenatal Bisphenol A exposure on male reproductive function at 20–22 years of age. Reprod. Biomed. Online. 2018;36:340–347. doi: 10.1016/j.rbmo.2017.11.009.
    1. Adoamnei E., Mendiola J., Vela-Soria F., Fernández M.F., Olea N., Jørgensen N., Swan S.H., Torres-Cantero A.M. Urinary bisphenol A concentrations are associated with reproductive parameters in young men. Environ. Res. 2018;161:122–128. doi: 10.1016/j.envres.2017.11.002.
    1. Minatoya M., Sasaki S., Araki A., Miyashita C., Itoh S., Yamamoto J., Matsumura T., Mitsui T., Moriya K., Cho K., et al. Cord Blood Bisphenol A Levels and Reproductive and Thyroid Hormone Levels of Neonates: The Hokkaido Study on Environment and Children’s Health. Epidemiology. 2017;28:S3–S9. doi: 10.1097/EDE.0000000000000716.
    1. Vitku J., Heracek J., Sosvorova L., Hampl R., Chlupacova T., Hill M., Sobotka V., Bicikova M., Starka L. Associations of bisphenol A and polychlorinated biphenyls with spermatogenesis and steroidogenesis in two biological fluids from men attending an infertility clinic. Environ. Int. 2016;89–90:166–173. doi: 10.1016/j.envint.2016.01.021.
    1. Fernández M.F., Arrebola J.P., Jiménez-Díaz I., Sáenz J.M., Molina-Molina J.M., Ballesteros O., Kortenkamp A., Olea N. Bisphenol A and other phenols in human placenta from children with cryptorchidism or hypospadias. Reprod. Toxicol. 2016;59:89–95. doi: 10.1016/j.reprotox.2015.11.002.
    1. Chen Q., Yang H., Zhou N., Sun L., Bao H., Tan L., Chen H., Ling X., Zhang G., Huang L., et al. Phthalate exposure, even below US EPA reference doses, was associated with semen quality and reproductive hormones: Prospective MARHCS study in general population. Environ. Int. 2017;104:58–68. doi: 10.1016/j.envint.2017.04.005.
    1. Axelsson J., Rylander L., Rignell-Hydbom A., Lindh C.H., Jönsson B.A., Giwercman A. Prenatal phthalate exposure and reproductive function in young men. Environ. Res. 2015;138:264–270. doi: 10.1016/j.envres.2015.02.024.
    1. Bloom M.S., Whitcomb B.W., Chen Z., Ye A., Kannan K., Buck Louis G.M. Associations between urinary phthalate concentrations and semen quality parameters in a general population. Hum. Reprod. 2015;30:2645–2657. doi: 10.1093/humrep/dev219.
    1. Chiu Y.H., Gaskins A.J., Williams P.L., Mendiola J., Jørgensen N., Levine H., Hauser R., Swan S.H., Chavarro J.E. Intake of Fruits and Vegetables with Low-to-Moderate Pesticide Residues Is Positively Associated with Semen-Quality Parameters among Young Healthy Men. J. Nutr. 2016;146:1084–1092. doi: 10.3945/jn.115.226563.
    1. García J., Ventura M.I., Requena M., Hernández A.F., Parrón T., Alarcón R. Association of reproductive disorders and male congenital anomalies with environmental exposure to endocrine active pesticides. Reprod. Toxicol. 2017;71:95–100. doi: 10.1016/j.reprotox.2017.04.011.
    1. Winston J.J., Emch M., Meyer R.E., Langlois P., Weyer P., Mosley B., Olshan A.F., Band L.E., Luben T.J., National Birth Defects Prevention Study Hypospadias and maternal exposure to atrazine via drinking water in the National Birth Defects Prevention study. Environ. Health. 2016;15:76. doi: 10.1186/s12940-016-0161-9.
    1. Daoud S., Sellami A., Bouassida M., Kebaili S., Ammar Keskes L., Rebai T., Chakroun Feki N. Routine assessment of occupational exposure and its relation to semen quality in infertile men: A cross-sectional study. Turk. J. Med. Sci. 2017;47:902–907. doi: 10.3906/sag-1605-47.
    1. Cremonese C., Piccoli C., Pasqualotto F., Clapauch R., Koifman R.J., Koifman S., Freire C. Occupational exposure to pesticides, reproductive hormone levels and sperm quality in young Brazilian men. Reprod. Toxicol. 2017;67:174–185. doi: 10.1016/j.reprotox.2017.01.001.
    1. Koskenniemi J.J., Virtanen H.E., Kiviranta H., Damgaard I.N., Matomäki J., Thorup J.M., Hurme T., Skakkebaek N.E., Main K.M., Toppari J. Association between levels of persistent organic pollutants in adipose tissue and cryptorchidismin early childhood: A case-control study. Environ. Health. 2015;14:78. doi: 10.1186/s12940-015-0065-0.
    1. Soto A.M., Sonnenschein C. The somatic mutation theory of cancer: Growing problems with the paradigm? Bioessays. 2004;26:1097–1107. doi: 10.1002/bies.20087.
    1. Hanahan D., Weinberg R.A. The hallmarks of cancer. Cell. 2000;100:57–70. doi: 10.1016/S0092-8674(00)81683-9.
    1. Rey O., Danchin E., Mirouze M., Loot C., Blanchet S. Adaptation to Global Change: A Transposable Element-Epigenetics Perspective. Trends Ecol. Evol. 2016;31:514–526. doi: 10.1016/j.tree.2016.03.013.
    1. Knudson A. Mutation and cancer: Statistical study of retinoblastoma. Proc. Natl. Acad. Sci. USA. 1971;68:820–823. doi: 10.1073/pnas.68.4.820.
    1. Hanson M.A., Gluckman P.D. Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology? Physiol. Rev. 2014;94:1027–1076. doi: 10.1152/physrev.00029.2013.
    1. Soto A.M., Maffini M.V., Sonnenschein C. Neoplasia as development gone awry: The role of endocrine disruptors. Int. J. Androl. 2008;31:288–293. doi: 10.1111/j.1365-2605.2007.00834.x.
    1. Melnick R.L., Huff J. Lorenzo Tomatis and primary prevention of environmental cancer. Environ. Health. 2011;10:S14. doi: 10.1186/1476-069X-10-S1-S14.
    1. Tomatis L. Prenatal exposure to chemical carcinogens and its effect on subsequent generations. Natl. Cancer Inst. Monogr. 1979;51:159–184.
    1. Huo D., Anderson D., Palmer J.R., Herbst A.L. Incidence rates and risks of diethylstilbestrol-related clear-cell adenocarcinoma of the vagina and cervix: Update after 40-year follow-up. Gynecol. Oncol. 2017;146:566–571. doi: 10.1016/j.ygyno.2017.06.028.
    1. Herbst A.L., Ulfelder H., Poskanzer D.C. Adenocarcinoma of the vagina. Association of maternal stilbestrol therapy with tumor appearance in young women. N. Engl. J. Med. 1971;284:878–881. doi: 10.1056/NEJM197104222841604.
    1. Yamasaki H., Loktionov A., Tomatis L. Perinatal and multigenerational effect of carcinogens: Possible contribution to determination of cancer susceptibility. Environ. Health Perspect. 1992;98:39–43. doi: 10.1289/ehp.929839.
    1. Miller C., Degenhardt K., Sassoon D.A. Fetal exposure to DES results in de-regulation of Wnt7a during uterine morphogenesis. Nat. Genet. 1998;20:228–230. doi: 10.1038/3027.
    1. Block K., Kardana A., Igarashi P., Taylor H.S. In utero diethylstilbestrol (DES) exposure alters Hox gene expression in the developing mullerian system. FASEB J. 2000;14:1101–1108. doi: 10.1096/fasebj.14.9.1101.
    1. Hussain I., Bhan A., Ansari I.K., Deba P., Bobzeanb S.A.M., Perrotti L.I., Mandal S.S. Bisphenol-A induces expression of HOXC6, an estrogen-regulated homeobox-containing gene associated with breast cancer. Biochim. Biophys. Acta. 2015;1849:697–708. doi: 10.1016/j.bbagrm.2015.02.003.
    1. Cook J.D., Davis B.J., Cai S.L., Barrett J.C., Conti C.J., Walker C.L. Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance. Proc. Natl. Acad. Sci. USA. 2005;102:8644–8649. doi: 10.1073/pnas.0503218102.
    1. Padmanabhan R., Hendry I.R., Knapp J.R., Shuai B., Hendry W.J. Altered microRNA expression patterns during the initiation and promotion stages of neonatal diethylstilbestrol-induced dysplasia/neoplasia in the hamster (Mesocricetus auratus) uterus. Cell. Biol. Toxicol. 2017;33:483–500. doi: 10.1007/s10565-017-9389-6.
    1. Vorderstrasse B.A., Fenton S.E., Bohn A.A., Cundiff J.A., Lawrence B.P. A novel effect of dioxin: Exposure during pregnancy severely impairs mammary gland differentiation. Toxicol. Sci. 2004;78:248–257. doi: 10.1093/toxsci/kfh062.
    1. Steenland K., Bertazzi P., Baccarelli A., Kogevinas M. Dioxin Revisited: Developments since the 1997 IARC Classification of Dioxin as a Human Carcinogen. Environ. Health Perspect. 2004;112:1265–1268. doi: 10.1289/ehp.7219.
    1. Moral R., Wang R., Russo I.H., Lamartiniere C.A., Pereira J., Russo J. Effect of prenatal exposure to the endocrine disruptor bisphenol a on mammary gland morphology and gene expression signature. J. Endocrinol. 2008;196:101–112. doi: 10.1677/JOE-07-0056.
    1. Gray J.M., Rasanayagam S., Engel C., Rizzo J. State of the evidence 2017: An update on the connection between breast cancer and the environment. Environ. Health. 2017;16:94. doi: 10.1186/s12940-017-0287-4.
    1. Giulivo M., Lopez de Alda M., Capri E., Barceló D. Human exposure to endocrine disrupting compounds: Their role in reproductive systems, metabolic syndrome and breast cancer. A review. Environ. Res. 2016;151:251–264. doi: 10.1016/j.envres.2016.07.011.
    1. Prins G.S., Tang W.Y., Belmonte J., Ho S.M. Perinatal exposure to oestradiol and bisphenol A alters the prostate epigenome and increases susceptibility to carcinogenesis. Basic Clin. Pharmacol. Toxicol. 2008;102:134–138. doi: 10.1111/j.1742-7843.2007.00166.x.
    1. Doherty L.F., Bromer J.G., Zhou Y., Aldad T.S., Taylor H.S. In utero exposure to diethylstilbestrol (DES) or bisphenol-A (BPA) increases EZH2 expression in the mammary gland: An epigenetic mechanism linking endocrine disruptors to breast cancer. Horm. Cancer. 2010;1:146–155. doi: 10.1007/s12672-010-0015-9.
    1. Di Donato M., Cernera G., Giovannelli P., Galasso G., Bilancio A., Migliaccio A., Castoria G. Recent advances on bisphenol-A and endocrine disruptor effects on human prostate cancer. Mol. Cell. Endocrinol. 2017;457:35–42. doi: 10.1016/j.mce.2017.02.045.
    1. Santangeli S., Maradonna F., Olivotto I., Piccinetti C.C., Gioacchini G., Carnevali O. Effects of BPA on female reproductive function: The involvement of epigenetic mechanism. Gen. Comp. Endocrinol. 2017;245:122–126. doi: 10.1016/j.ygcen.2016.08.010.
    1. Baccarelli A., Hirt C., Pesatori A.C., Consonni D., Patterson D.G., Jr., Bertazzi P.A., Dölken G., Landi M.T. t(14;18) translocations in lymphocytes of healthy dioxin-exposed individuals from Seveso, Italy. Carcinogenesis. 2006;27:2001–2007. doi: 10.1093/carcin/bgl011.
    1. Agopian J., Navarro J.M., Gac A.C., Lecluse Y., Briand M., Grenot P., Gauduchon P., Ruminy P., Lebailly P., Nadel B., et al. Agricultural pesticide exposure and the molecular connection to lymphomagenesis. J. Exp. Med. 2009;206:1473–1483. doi: 10.1084/jem.20082842.

Source: PubMed

Подписаться