Placental Responses to Changes in the Maternal Environment Determine Fetal Growth

Kris Genelyn Dimasuay, Philippe Boeuf, Theresa L Powell, Thomas Jansson, Kris Genelyn Dimasuay, Philippe Boeuf, Theresa L Powell, Thomas Jansson

Abstract

Placental responses to maternal perturbations are complex and remain poorly understood. Altered maternal environment during pregnancy such as hypoxia, stress, obesity, diabetes, toxins, altered nutrition, inflammation, and reduced utero-placental blood flow may influence fetal development, which can predispose to diseases later in life. The placenta being a metabolically active tissue responds to these perturbations by regulating the fetal supply of nutrients and oxygen and secretion of hormones into the maternal and fetal circulation. We have proposed that placental nutrient sensing integrates maternal and fetal nutritional cues with information from intrinsic nutrient sensing signaling pathways to balance fetal demand with the ability of the mother to support pregnancy by regulating maternal physiology, placental growth, and placental nutrient transport. Emerging evidence suggests that the nutrient-sensing signaling pathway mechanistic target of rapamycin (mTOR) plays a central role in this process. Thus, placental nutrient sensing plays a critical role in modulating maternal-fetal resource allocation, thereby affecting fetal growth and the life-long health of the fetus.

Keywords: fetal programming; maternal–fetal exchange; mechanistic target of rapamycin; placental nutrient sensing; pregnancy; syncytiotrophoblast.

Figures

Figure 1
Figure 1
Placental nutrient sensing model. The placenta integrates maternal signals with information from nutrient sensing signaling pathways such as mechanistic target of rapamycin (mTOR) to regulate placental function. As a result, fetal growth is matched to the ability of the maternal supply line to allocate resources to the fetus. Thus, the placental responses to maternal signals influence fetal growth and the long-term health of the offspring.
Figure 2
Figure 2
Placental mTOR as a nutrient sensing signaling pathway. mTOR integrates maternal signals such as nutrients and growth factors to modulate the transport of nutrients from the maternal to the fetal circulation. mTORC1 modulates the trafficking of AA transporters possibly through differential ubiquitination mediated by NEDD4-2. Inhibition of NEDD4-2 will result in increased localization of AA transporters in the plasma membrane (Rosario et al., , ; Chen et al., 2015).

References

    1. Abrams E. T., Brown H., Chensue S. W., Turner G. D., Tadesse E., Lema V. M., et al. . (2003). Host response to malaria during pregnancy: placental monocyte recruitment is associated with elevated beta chemokine expression. J. Immunol. 170, 2759–2764. 10.4049/jimmunol.170.5.2759
    1. Anderson A. H., Fennessey P. V., Meschia G., Wilkening R. B., Battaglia F. C. (1997). Placental transport of threonine and its utilization in the normal and growth-restricted fetus. Am. J. Physiol. 272, E892–E900.
    1. Armitage J. A., Khan I. Y., Taylor P. D., Nathanielsz P. W., Poston L. (2004). Developmental programming of the metabolic syndrome by maternal nutritional imbalance: how strong is the evidence from experimental models in mammals? J. Physiol. 561, 355–377. 10.1113/jphysiol.2004.072009
    1. Audette M. C., Challis J. R., Jones R. L., Sibley C. P., Matthews S. G. (2011). Antenatal dexamethasone treatment in midgestation reduces system A-mediated transport in the late-gestation murine placenta. Endocrinology 152, 3561–3570. 10.1210/en.2011-0104
    1. Aye I. L., Gao X., Weintraub S. T., Jansson T., Powell T. L. (2014a). Adiponectin inhibits insulin function in primary trophoblasts by PPARalpha-mediated ceramide synthesis. Mol. Endocrinol. 28, 512–524. 10.1210/me.2013-1401
    1. Aye I. L., Lager S., Ramirez V. I., Gaccioli F., Dudley D. J., Jansson T., et al. . (2014b). Increasing maternal body mass index is associated with systemic inflammation in the mother and the activation of distinct placental inflammatory pathways. Biol. Reprod. 90, 129. 10.1095/biolreprod.113.116186
    1. Aye I. L. M. H., Jansson T., Powell T. L. (2013b). Interleukin-1 beta inhibits insulin signaling and prevents insulin-stimulated system A amino acid transport in primary human trophoblasts. Mol. Cell. Endocrinol. 381, 46–55. 10.1016/j.mce.2013.07.013
    1. Aye I. L., Powell T. L., Jansson T. (2013a). Review: adiponectin–the missing link between maternal adiposity, placental transport and fetal growth? Placenta 34Suppl., S40–S45. 10.1016/j.placenta.2012.11.024
    1. Aye I. L., Rosario F. J., Powell T. L., Jansson T. (2015). Adiponectin supplementation in pregnant mice prevents the adverse effects of maternal obesity on placental function and fetal growth. Proc. Natl. Acad. Sci. U.S.A. 112, 12858–12863. 10.1073/pnas.1515484112
    1. Barker D. J., Osmond C., Golding J., Kuh D., Wadsworth M. E. (1989). Growth in utero, blood pressure in childhood and adult life, and mortality from cardiovascular disease. BMJ 298, 564–567. 10.1136/bmj.298.6673.564
    1. Barker D. J. P., Osmond C. (1986). Infant-mortality, childhood nutrition, and ischemic-heart-disease in England and Wales. Lancet 1, 1077–1081. 10.1016/S0140-6736(86)91340-1
    1. Baumann M. U., Schneider H., Malek A., Palta V., Surbek D. V., Sager R., et al. . (2014). Regulation of human trophoblast GLUT1 glucose transporter by insulin-like growth factor I (IGF-I). PLoS ONE 9:e106037. 10.1371/journal.pone.0106037
    1. Boeuf P., Aitken E. H., Chandrasiri U., Chua C. L., McInerney B., McQuade L., et al. . (2013). Plasmodium falciparum malaria elicits inflammatory responses that dysregulate placental amino acid transport. PLoS Pathog. 9:e1003153. 10.1371/journal.ppat.1003153
    1. Bouyou-Akotet M. K., Kombila M., Kremsner P. G., Mavoungou E. (2004). Cytokine profiles in peripheral, placental and cord blood in pregnant women from an area endemic for Plasmodium falciparum. Eur. Cytokine Netw. 15, 120–125.
    1. Brugarolas J., Lei K., Hurley R. L., Manning B. D., Reiling J. H., Hafen E., et al. . (2004). Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 18, 2893–2904. 10.1101/gad.1256804
    1. Burton G. J. (2010). The influence of the intrauterine environment on human placental development. J. Reprod. Immunol. 86, 81–82. 10.1016/j.jri.2010.08.006
    1. Cetin I., Corbetta C., Sereni L. P., Marconi A. M., Bozzetti P., Pardi G., et al. . (1990). Umbilical amino acid concentrations in normal and growth-retarded fetuses sampled in utero by cordocentesis. Am. J. Obstet. Gynecol. 162, 253–261. 10.1016/0002-9378(90)90860-A
    1. Challier J. C., Basu S., Bintein T., Minium J., Hotmire K., Catalano P. M., et al. . (2008). Obesity in pregnancy stimulates macrophage accumulation and inflammation in the placenta. Placenta 29, 274–281. 10.1016/j.placenta.2007.12.010
    1. Chandrasiri U. P., Chua C. L., Umbers A. J., Chaluluka E., Glazier J. D., Rogerson S. J., et al. . (2014). Insight into the pathogenesis of fetal growth restriction in placental malaria: decreased placental glucose transporter isoform 1 expression. J. Infect. Dis. 209, 1663–1667. 10.1093/infdis/jit803
    1. Chen Y. Y., Rosario F. J., Shehab M. A., Powell T. L., Gupta M. B., Jansson T. (2015). Increased ubiquitination and reduced plasma membrane trafficking of placental amino acid transporter SNAT-2 in human IUGR. Clin. Sci. 129, 1131–1141. 10.1042/CS20150511
    1. Dahlgren J., Nilsson C., Jennische E., Ho H. P., Eriksson E., Niklasson A., et al. . (2001). Prenatal cytokine exposure results in obesity and gender-specific programming. Am. J. Physiol. Endocrinol. Metab. 281, E326–E334.
    1. de Boo H. A., Eremia S. C., Bloomfield F. H., Oliver M. H., Harding J. E. (2008). Treatment of intrauterine growth restriction with maternal growth hormone supplementation in sheep. Am. J. Obstet. Gynecol. 199, e551–e559. 10.1016/j.ajog.2008.04.035
    1. Desai M., ter Kuile F. O., Nosten F., McGready R., Asamoa K., Brabin B., et al. . (2007). Epidemiology and burden of malaria in pregnancy. Lancet Infect. Dis. 7, 93–104. 10.1016/S1473-3099(07)70021-X
    1. Desoye G., Hartmann M., Blaschitz A., Dohr G., Hahn T., Kohnen G., et al. . (1994). Insulin receptors in syncytiotrophoblast and fetal endothelium of human placenta. Immunohistochemical evidence for developmental changes in distribution pattern. Histochemistry 101, 277–285. 10.1007/BF00315915
    1. de Vrijer B., Regnault T. R., Wilkening R. B., Meschia G., Battaglia F. C. (2004). Placental uptake and transport of ACP, a neutral nonmetabolizable amino acid, in an ovine model of fetal growth restriction. Am. J. Physiol. Endocrinol. Metab. 287, E1114–E1124. 10.1152/ajpendo.00259.2004
    1. Díaz P., Powell T. L., Jansson T. (2014). The role of placental nutrient sensing in maternal-fetal resource allocation. Biol. Reprod. 91, 82. 10.1095/biolreprod.114.121798
    1. Ebenbichler C. F., Kaser S., Laimer M., Wolf H. J., Patsch J. R., Illsley N. P. (2002). Polar expression and phosphorylation of human leptin receptor isoforms in paired, syncytial, microvillous and basal membranes from human term placenta. Placenta 23, 516–521. 10.1053/plac.2002.0836
    1. Economides D. L., Nicolaides K. H., Gahl W. A., Bernardini I., Evans M. I. (1989). Plasma amino acids in appropriate- and small-for-gestational-age fetuses. Am. J. Obstet. Gynecol. 161, 1219–1227. 10.1016/0002-9378(89)90670-4
    1. Fang J., Furesz T. C., Lurent R. S., Smith C. H., Fant M. E. (1997). Spatial polarization of insulin-like growth factor receptors on the human syncytiotrophoblast. Pediatr. Res. 41, 258–265. 10.1203/00006450-199702000-00017
    1. Forsdahl A. (1977). Are poor living conditions in childhood and adolescence an important risk factor for arteriosclerotic heart disease? Br. J. Prev. Soc. Med. 31, 91–95. 10.1136/jech.31.2.91
    1. Fowden A. L., Forhead A. J., Sferruzzi-Perri A. N., Burton G. J., Vaughan O. R. (2015). Review: endocrine regulation of placental phenotype. Placenta 36(Suppl. 1), S50–S59. 10.1016/j.placenta.2014.11.018
    1. Gaccioli F., Lager S., Powell T. L., Jansson T. (2013). Placental transport in response to altered maternal nutrition. J. Dev. Orig. Health Dis. 4, 101–115. 10.1017/S2040174412000529
    1. Ganguly A., Collis L., Devaskar S. U. (2012). Placental glucose and amino acid transport in calorie-restricted wild-type and Glut3 null heterozygous mice. Endocrinology 153, 3995–4007. 10.1210/en.2011-1973
    1. Giussani D. A., Salinas C. E., Villena M., Blanco C. E. (2007). The role of oxygen in prenatal growth: studies in the chick embryo. J. Physiol. 585, 911–917. 10.1113/jphysiol.2007.141572
    1. Glazier J. D., Cetin I., Perugino G., Ronzoni S., Grey A. M., Mahendran D., et al. . (1997). Association between the activity of the system A amino acid transporter in the microvillous plasma membrane of the human placenta and severity of fetal compromise in intrauterine growth restriction. Pediatr. Res. 42, 514–519. 10.1203/00006450-199710000-00016
    1. Glazier J. D., Sibley C. P., Carter A. M. (1996). Effect of fetal growth restriction on system A amino acid transporter activity in the maternal facing plasma membrane of rat syncytiotrophoblast. Pediatr. Res. 40, 325–329. 10.1203/00006450-199608000-00022
    1. Gluckman P. D., Hanson M. A. (2004). Living with the past: evolution, development, and patterns of disease. Science 305, 1733–1736. 10.1126/science.1095292
    1. Guyatt H. L., Snow R. W. (2004). Impact of malaria during pregnancy on low birth weight in sub-Saharan Africa. Clin. Microbiol. Rev. 17, 760–769. 10.1128/CMR.17.4.760-769.2004
    1. Hales C. N., Barker D. J. P., Clark P. M. S., Cox L. J., Fall C., Osmond C., et al. . (1991). Fetal and infant growth and impaired glucose-tolerance at age 64. Br. Med. J. 303, 1019–1022. 10.1136/bmj.303.6809.1019
    1. Hernandez-Valencia M., Zarate A., Ochoa R., Fonseca M. E., Amato D., De Jesus Ortiz M. (2001). Insulin-like growth factor I, epidermal growth factor and transforming growth factor beta expression and their association with intrauterine fetal growth retardation, such as development during human pregnancy. Diabetes Obes. Metab. 3, 457–462. 10.1046/j.1463-1326.2001.00168.x
    1. Holmes R., Montemagno R., Jones J., Preece M., Rodeck C., Soothill P. (1997). Fetal and maternal plasma insulin-like growth factors and binding proteins in pregnancies with appropriate or retarded fetal growth. Early Hum. Dev. 49, 7–17. 10.1016/S0378-3782(97)01867-7
    1. Ingvorsen C., Brix S., Ozanne S. E., Hellgren L. I. (2015). The effect of maternal inflammation on foetal programming of metabolic disease. Acta Physiol. 214, 440–449. 10.1111/apha.12533
    1. Ingvorsen C., Thysen A. H., Fernandez-Twinn D., Nordby P., Nielsen K. F., Ozanne S. E., et al. . (2014). Effects of pregnancy on obesity-induced inflammation in a mouse model of fetal programming. Int. J. Obes. 38, 1282–1289. 10.1038/ijo.2014.69
    1. Inoki K., Zhu T., Guan K. L. (2003). TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577–590. 10.1016/S0092-8674(03)00929-2
    1. Ioannidis L. J., Nie C. Q., Hansen D. S. (2014). The role of chemokines in severe malaria: more than meets the eye. Parasitology 141, 602–613. 10.1017/S0031182013001984
    1. Jansson N., Greenwood S. L., Johansson B. R., Powell T. L., Jansson T. (2003). Leptin stimulates the activity of the system A amino acid transporter in human placental villous fragments. J. Clin. Endocrinol. Metab. 88, 1205–1211. 10.1210/jc.2002-021332
    1. Jansson N., Nilsfelt A., Gellerstedt M., Wennergren M., Rossander-Hulthén L., Powell T. L., et al. . (2008). Maternal hormones linking maternal body mass index and dietary intake to birth weight. Am. J. Clin. Nutr. 87, 1743–1749.
    1. Jansson N., Pettersson J., Haafiz A., Ericsson A., Palmberg I., Tranberg M., et al. . (2006). Down-regulation of placental transport of amino acids precedes the development of intrauterine growth restriction in rats fed a low protein diet. J. Physiol. Lond. 576, 935–946. 10.1113/jphysiol.2003.550004
    1. Jansson N., Rosario F. J., Gaccioli F., Lager S., Jones H. N., Roos S., et al. . (2013). Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J. Clin. Endocrinol. Metab. 98, 105–113. 10.1210/jc.2012-2667
    1. Jansson T., Aye I. L., Goberdhan D. C. (2012). The emerging role of mTORC1 signaling in placental nutrient-sensing. Placenta 33(Suppl. 2), e23–e29. 10.1016/j.placenta.2012.05.010
    1. Jansson T., Ekstrand Y., Björn C., Wennergren M., Powell T. L. (2002a). Alterations in the activity of placental amino acid transporters in pregnancies complicated by diabetes. Diabetes 51, 2214–2219. 10.2337/diabetes.51.7.2214
    1. Jansson T., Persson E. (1990). Placental-transfer of glucose and amino-acids in intrauterine growth-retardation – studies with substrate-analogs in the awake guinea-pig. Pediatr. Res. 28, 203–208. 10.1203/00006450-199009000-00007
    1. Jansson T., Powell T. L. (2006). Human placental transport in altered fetal growth: does the placenta function as a nutrient sensor? Rev. Placenta 27, S91–S97. 10.1016/j.placenta.2005.11.010
    1. Jansson T., Powell T. L. (2013). Role of placental nutrient sensing in developmental programming. Clin. Obstet. Gynecol. 56, 591–601. 10.1097/GRF.0b013e3182993a2e
    1. Jansson T., Scholtbach V., Powell T. L. (1998). Placental transport of leucine and lysine is reduced in intrauterine growth restriction. Pediatr. Res. 44, 532–537. 10.1203/00006450-199810000-00011
    1. Jansson T., Wennergren M., Illsley N. P. (1993). Glucose transporter protein expression in human placenta throughout gestation and in intrauterine growth retardation. J. Clin. Endocrinol. Metab. 77, 1554–1562.
    1. Jansson T., Wennergren M., Powell T. L. (1999). Placental glucose transport and GLUT 1 expression in insulin-dependent diabetes. Am. J. Obstet. Gynecol. 180, 163–168. 10.1016/S0002-9378(99)70169-9
    1. Jansson T., Ylvén K., Wennergren M., Powell T. L. (2002b). Glucose transport and system A activity in syncytiotrophoblast microvillous and basal plasma membranes in intrauterine growth restriction. Placenta 23, 392–399. 10.1053/plac.2002.0826
    1. Jiang H., Xun P. C., Luo G. H., Wang Q. W., Cai Y. Q., Zhang Y. Y., et al. . (2009). Levels of insulin-like growth factors and their receptors in placenta in relation to macrosomia. Asia Pac. J. Clin. Nutr. 18, 171–178.
    1. Jones H. N., Crombleholme T., Habli M. (2013). Adenoviral-mediated placental gene transfer of IGF-1 corrects placental insufficiency via enhanced placental glucose transport mechanisms. PLoS ONE 8:e74632. 10.1371/journal.pone.0074632
    1. Jones H. N., Jansson T., Powell T. L. (2009a). IL-6 stimulates system A amino acid transporter activity in trophoblast cells through STAT3 and increased expression of SNAT2. Am. J. Physiol. Cell Physiol. 297, C1228–C1235. 10.1152/ajpcell.00195.2009
    1. Jones H. N., Jansson T., Powell T. L. (2010). Full-length adiponectin attenuates insulin signaling and inhibits insulin-stimulated amino Acid transport in human primary trophoblast cells. Diabetes 59, 1161–1170. 10.2337/db09-0824
    1. Jones H. N., Powell T. L., Jansson T. (2007). Regulation of placental nutrient transport–a review. Placenta 28, 763–774. 10.1016/j.placenta.2007.05.002
    1. Jones H. N., Woollett L. A., Barbour N., Prasad P. D., Powell T. L., Jansson T. (2009b). High-fat diet before and during pregnancy causes marked up-regulation of placental nutrient transport and fetal overgrowth in C57/BL6 mice. FASEB J. 23, 271–278. 10.1096/fj.08-116889
    1. Kabyemela E. R., Muehlenbachs A., Fried M., Kurtis J. D., Mutabingwa T. K., Duffy P. E. (2008). Maternal peripheral blood level of IL-10 as a marker for inflammatory placental malaria. Malar. J. 7:26. 10.1186/1475-2875-7-26
    1. Karl P. I. (1995). Insulin-like growth factor-1 stimulates amino acid uptake by the cultured human placental trophoblast. J. Cell. Physiol. 165, 83–88. 10.1002/jcp.1041650111
    1. Karl P. I., Alpy K. L., Fisher S. E. (1992). Amino acid transport by the cultured human placental trophoblast: effect of insulin on AIB transport. Am. J. Physiol. 262, C834–C839.
    1. Kavitha J. V., Rosario F. J., Nijland M. J., McDonald T. J., Wu G., Kanai Y., et al. . (2014). Down-regulation of placental mTOR, insulin/IGF-I signaling, and nutrient transporters in response to maternal nutrient restriction in the baboon. FASEB J. 28, 1294–1305. 10.1096/fj.13-242271
    1. Keswani S. G., Balaji S., Katz A. B., King A., Omar K., Habli M., et al. . (2015). Intraplacental gene therapy with Ad-IGF-1 corrects naturally occurring rabbit model of intrauterine growth restriction. Hum. Gene Ther. 26, 172–182. 10.1089/hum.2014.065
    1. Krishna U., Bhalerao S. (2011). Placental insufficiency and fetal growth restriction. J. Obstet. Gynaecol. India 61, 505–511. 10.1007/s13224-011-0092-x
    1. Lauszus F. F., Klebe J. G., Flyvbjerg A. (2001). Macrosomia associated with maternal serum insulin-like growth factor-I and -II in diabetic pregnancy. Obstet. Gynecol. 97, 734–741. 10.1016/S0029-7844(01)01189-9
    1. Laviola L., Perrini S., Belsanti G., Natalicchio A., Montrone C., Leonardini A., et al. . (2005). Intrauterine growth restriction in humans is associated with abnormalities in placental insulin-like growth factor signaling. Endocrinology 146, 1498–1505. 10.1210/en.2004-1332
    1. Liu L., Harding J. E., Evans P. C., Gluckman P. D. (1994). Maternal insulin-like growth factor-I infusion alters feto-placental carbohydrate and protein metabolism in pregnant sheep. Endocrinology 135, 895–900.
    1. Magnusson A. L., Waterman I. J., Wennergren M., Jansson T., Powell T. L. (2004). Triglyceride hydrolase activities and expression of fatty acid binding proteins in the human placenta in pregnancies complicated by intrauterine growth restriction and diabetes. J. Clin. Endocrinol. Metab. 89, 4607–4614. 10.1210/jc.2003-032234
    1. Mahendran D., Donnai P., Glazier J. D., D'souza S. W., Boyd R. D., Sibley C. P. (1993). Amino acid (system A) transporter activity in microvillous membrane vesicles from the placentas of appropriate and small for gestational age babies. Pediatr. Res. 34, 661–665. 10.1203/00006450-199311000-00019
    1. Malandro M. S., Beveridge M. J., Kilberg M. S., Novak D. A. (1996). Effect of low-protein diet-induced intrauterine growth retardation on rat placental amino acid transport. Am. J. Physiol. 271, C295–C303.
    1. Mehta A. R., Mehta P. R. (2008). The hypoxia of high altitude causes restricted fetal growth in chick embryos with the extent of this effect depending on maternal altitudinal status. J. Physiol. 586, 1469–1471. 10.1113/jphysiol.2008.151332
    1. Nelson D. M., Smith S. D., Furesz T. C., Sadovsky Y., Ganapathy V., Parvin C. A., et al. . (2003). Hypoxia reduces expression and function of system A amino acid transporters in cultured term human trophoblasts. Am. J. Physiol. Cell Physiol. 284, C310–C315. 10.1152/ajpcell.00253.2002
    1. Nilsson C., Larsson B. M., Jennische E., Eriksson E., Björntorp P., York D. A., et al. . (2001). Maternal endotoxemia results in obesity and insulin resistance in adult male offspring. Endocrinology 142, 2622–2630. 10.1210/en.142.6.2622
    1. Nitzan M., Orloff S., Schulman J. D. (1979). Placental transfer of analogs of glucose and amino acids in experimental intrauterine growth retardation. Pediatr. Res. 13, 100–103. 10.1203/00006450-197902000-00003
    1. Norberg S., Powell T. L., Jansson T. (1998). Intrauterine growth restriction is associated with a reduced activity of placental taurine transporters. Pediatr. Res. 44, 233–238. 10.1203/00006450-199808000-00016
    1. Ordi J., Ismail M. R., Ventura P. J., Kahigwa E., Hirt R., Cardesa A., et al. . (1998). Massive chronic intervillositis of the placenta associated with malaria infection. Am. J. Surg. Pathol. 22, 1006–1011. 10.1097/00000478-199808000-00011
    1. Padoan A., Rigano S., Ferrazzi E., Beaty B. L., Battaglia F. C., Galan H. L. (2004). Differences in fat and lean mass proportions in normal and growth-restricted fetuses. Am. J. Obstet. Gynecol. 191, 1459–1464. 10.1016/j.ajog.2004.06.045
    1. Pantham P., Aye I. L., Powell T. L. (2015a). Inflammation in maternal obesity and gestational diabetes mellitus. Placenta 36, 709–715. 10.1016/j.placenta.2015.04.006
    1. Pantham P., Rosario F. J., Njiland M., Cheung A., Nathanielsz P. W., Powell T. L., et al. . (2015b). Reduced placental amino acid transport in response to maternal nutrient restriction in the baboon. Am. J. Physiol. Regul. Integr. Comp. Physiol. 309, R740–R746. 10.1152/ajpregu.00161.2015
    1. Paolini C. L., Marconi A. M., Ronzoni S., Di Noio M., Fennessey P. V., Pardi G., et al. . (2001). Placental transport of leucine, phenylalanine, glycine, and proline in intrauterine growth-restricted pregnancies. J. Clin. Endocrinol. Metab. 86, 5427–5432. 10.1210/jcem.86.11.8036
    1. Ravelli A. C. J., van der Meulen J. H. P., Michels R. P. J., Osmond C., Barker D. J. P., Hales C. N., et al. . (1998). Glucose tolerance in adults after prenatal exposure to famine. Lancet 351, 173–177. 10.1016/S0140-6736(97)07244-9
    1. Reid G. J., Lane R. H., Flozak A. S., Simmons R. A. (1999). Placental expression of glucose transporter proteins 1 and 3 in growth-restricted fetal rats. Am. J. Obstet. Gynecol. 180, 1017–1023. 10.1016/S0002-9378(99)70675-7
    1. Rogerson S. J., Brown H. C., Pollina E., Abrams E. T., Tadesse E., Lema V. M., et al. . (2003). Placental tumor necrosis factor alpha but not gamma interferon is associated with placental malaria and low birth weight in Malawian women. Infect. Immun. 71, 267–270. 10.1128/IAI.71.1.267-270.2003
    1. Rogerson S. J., Hviid L., Duffy P. E., Leke R. F., Taylor D. W. (2007). Malaria in pregnancy: pathogenesis and immunity. Lancet Infect. Dis. 7, 105–117. 10.1016/S1473-3099(07)70022-1
    1. Roos S., Jansson N., Palmberg I., Säljö K., Powell T. L., Jansson T. (2007). Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth. J. Physiol. 582, 449–459. 10.1113/jphysiol.2007.129676
    1. Roos S., Kanai Y., Prasad P. D., Powell T. L., Jansson T. (2009). Regulation of placental amino acid transporter activity by mammalian target of rapamycin. Am. J. Physiol. Cell Physiol. 296, C142–C150. 10.1152/ajpcell.00330.2008
    1. Rosario F. J., Dimasuay K. G., Kanai Y., Powell T. L., Jansson T. (2015a). Regulation of amino acid transporter trafficking by mTORC1 in primary human trophoblast cells is mediated by the ubiquitin ligase Nedd4-2. Clin Sci (Lond). [Epub ahead of print]. 10.1042/CS20150554.
    1. Rosario F. J., Jansson N., Kanai Y., Prasad P. D., Powell T. L., Jansson T. (2011). Maternal protein restriction in the rat inhibits placental insulin, mTOR, and STAT3 signaling and down-regulates placental amino acid transporters. Endocrinology 152, 1119–1129. 10.1210/en.2010-1153
    1. Rosario F. J., Kanai Y., Powell T. L., Jansson T. (2013). Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells. J. Physiol. 591, 609–625. 10.1113/jphysiol.2012.238014
    1. Rosario F. J., Kanai Y., Powell T. L., Jansson T. (2015b). Increased placental nutrient transport in a novel mouse model of maternal obesity with fetal overgrowth. Obesity 23, 1663–1670. 10.1002/oby.21165
    1. Rosario F. J., Schumacher M. A., Jiang J., Kanai Y., Powell T. L., Jansson T. (2012). Chronic maternal infusion of full-length adiponectin in pregnant mice down-regulates placental amino acid transporter activity and expression and decreases fetal growth. J. Physiol. (Lond). 590, 1495–1509. 10.1113/jphysiol.2011.226399
    1. Ross J. C., Fennessey P. V., Wilkening R. B., Battaglia F. C., Meschia G. (1996). Placental transport and fetal utilization of leucine in a model of fetal growth retardation. Am. J. Physiol. 270, E491–E503.
    1. Rosso P. (1977a). Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of alpha-amino isobutyric acid. J. Nutr. 107, 2002–2005.
    1. Rosso P. (1977b). Maternal-fetal exchange during protein malnutrition in the rat. Placental transfer of glucose and a nonmetabolizable glucose analog. J. Nutr. 107, 20006–20010.
    1. Sferruzzi-Perri A. N., Owens J. A., Pringle K. G., Roberts C. T. (2011a). The neglected role of insulin-like growth factors in the maternal circulation regulating fetal growth. J. Physiol. (Lond). 589, 7–20. 10.1113/jphysiol.2010.198622
    1. Sferruzzi-Perri A. N., Vaughan O. R., Coan P. M., Suciu M. C., Darbyshire R., Constancia M., et al. . (2011b). Placental-specific Igf2 deficiency alters developmental adaptations to undernutrition in mice. Endocrinology 152, 3202–3212. 10.1210/en.2011-0240
    1. Steketee R. W., Nahlen B. L., Parise M. E., Menendez C. (2001). The burden of malaria in pregnancy in malaria-endemic areas. Am. J. Trop. Med. Hyg. 64, 28–35.
    1. Suguitan A. L., Jr., Leke R. G., Fouda G., Zhou A., Thuita L., Metenou S., et al. . (2003). Changes in the levels of chemokines and cytokines in the placentas of women with Plasmodium falciparum malaria. J. Infect. Dis. 188, 1074–1082. 10.1086/378500
    1. Thongsong B., Subramanian R. K., Ganapathy V., Prasad P. D. (2005). Inhibition of amino acid transport system a by interleukin-1 beta in trophoblasts. J. Soc. Gynecol. Investig. 12, 495–503. 10.1016/j.jsgi.2005.06.008
    1. Thureen P. J., Trembler K. A., Meschia G., Makowski E. L., Wilkening R. B. (1992). Placental glucose transport in heat-induced fetal growth retardation. Am. J. Physiol. 263, R578–R585.
    1. Umbers A. J., Boeuf P., Clapham C., Stanisic D. I., Baiwog F., Mueller I., et al. . (2011). Placental malaria-associated inflammation disturbs the insulin-like growth factor axis of fetal growth regulation. J. Infect. Dis. 203, 561–569. 10.1093/infdis/jiq080
    1. Vaughan O. R., Sferruzzi-Perri A. N., Fowden A. L. (2012). Maternal corticosterone regulates nutrient allocation to fetal growth in mice. J. Physiol. (Lond). 590, 5529–5540. 10.1113/jphysiol.2012.239426
    1. von Versen-Höynck F., Rajakumar A., Parrott M. S., Powers R. W. (2009). Leptin affects system A amino acid transport activity in the human placenta: evidence for STAT3 dependent mechanisms. Placenta 30, 361–367. 10.1016/j.placenta.2009.01.004
    1. Wadsack C., Tabano S., Maier A., Hiden U., Alvino G., Cozzi V., et al. . (2007). Intrauterine growth restriction is associated with alterations in placental lipoprotein receptors and maternal lipoprotein composition. Am. J. Physiol. Endocrinol. Metab. 292, E476–E484. 10.1152/ajpendo.00547.2005
    1. Yildiz L., Avci B., Ingeç M. (2002). Umbilical cord and maternal blood leptin concentrations in intrauterine growth retardation. Clin. Chem. Lab. Med. 40, 1114–1117. 10.1515/cclm.2002.195
    1. Yung H. W., Calabrese S., Hynx D., Hemmings B. A., Cetin I., Charnock-Jones D. S., et al. . (2008). Evidence of placental translation inhibition and endoplasmic reticulum stress in the etiology of human intrauterine growth restriction. Am. J. Pathol. 173, 451–462. 10.2353/ajpath.2008.071193
    1. Zamudio S., Baumann M. U., Illsley N. P. (2006). Effects of chronic hypoxia in vivo on the expression of human placental glucose transporters. Placenta 27, 49–55. 10.1016/j.placenta.2004.12.010
    1. Zamudio S., Moore L. G. (2000). Altitude and fetal growth: current knowledge and future directions. Ultrasound Obstet. Gynecol. 16, 6–8. 10.1046/j.1469-0705.2000.00155.x

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