Role of microRNAs in premature ovarian insufficiency

Ying Guo, Junyan Sun, Dongmei Lai, Ying Guo, Junyan Sun, Dongmei Lai

Abstract

Premature ovarian insufficiency (POI) is a typical disorder of amenorrhea lasting for a minimum of 4 months. The typical characteristics comprised of declined estrogen and raised serum concentrations of follicle-stimulating hormone (FSH) in women <40-year-old, primarily originating from iatrogenic factors, karyotypic abnormalities, and genetic factors. However, the etiology of POI remains unknown in approximately 90% of cases. POI could lead to infertility, osteoporosis, cardiovascular disorder, and cognitive dysfunction. MicroRNAs (miRNAs) are a class of endogenous noncoding RNAs (ncRNAs) that can mediate post-translational silencing of the genes involved in the regulation of proliferation, differentiation, apoptosis, development, tumorigenesis, and hematopoiesis. Recently, the regulatory functions of miRNAs in the development of POI have been the topic of intensive research. The present review addresses the association of miRNAs' machinery genes (Dicer, Drosha, and XPO5) with POI and the miRNA expression profiles in the plasma of patients with POI. In addition, several specific miRNAs (miR-23a, miR-27a, miR-22-3p, miR-146a, miR-196a, miR-290-295, miR-423, and miR-608) related to POI are also examined in order to highlight the issues that deserve further investigation. A thorough understanding of the exact regulatory roles of miRNAs is imperative to gain novel insights into the etiology of idiopathic POI and offer new research directions in the field.

Keywords: Granulosa cells; MicroRNAs; Ovary; Primary ovarian insufficiency.

Figures

Fig. 1
Fig. 1
Schematic summary of health implications of POI. POI could lead to cognitive dysfunctions, such as memory impairment, dementia, social anxiety, depression, and Parkinsonism, increase thyroid disease risk, cardiovascular health issues including ischemic heart disease, endothelial dysfunction, and abnormal lipid profile, and cause reproductive and bone health disorders
Fig. 2
Fig. 2
Biosynthesis of miRNA and the machinery molecules associated with POI. MicroRNAs(miRNAs) are transcribed into primary miRNA (pri-miRNA) by RNA polymerase II and are cleaved by RNase III enzyme Drosha complex to generate the precursor miRNAs (pre-miRNAs) in the nucleus. Pre-miRNAs are transported to the cytoplasm by XPO5. Pre-miRNAs are further processed by RNase III enzyme, Dicer complex, to form mature miRNAs,which then are incorporated into the RNA-induced silencing complex (RISC), resulting in mRNA degradation or translational repression of target genes. XPO5 and Dicer were reported to be associated with POI and are marked by red arrows

References

    1. De Vos M, Devroey P, Fauser BC. Primary ovarian insufficiency. Lancet. 2010;376:911–21. doi: 10.1016/S0140-6736(10)60355-8.
    1. Vujovic S, Brincat M, Erel T, Gambacciani M, Lambrinoudaki I, Moen MH, Schenck-Gustafsson K, Tremollieres F, Rozenberg S, Rees M. EMAS position statement: Managing women with premature ovarian failure. Maturitas. 2010;67:91–3. doi: 10.1016/j.maturitas.2010.04.011.
    1. Coulam CB. Premature gonadal failure. Fertil Steril. 1982;38:645–55. doi: 10.1016/S0015-0282(16)46688-4.
    1. Podfigurna-Stopa A, Czyzyk A, Grymowicz M, Smolarczyk R, Katulski K, Czajkowski K, Meczekalski B. Premature ovarian insufficiency: the context of long-term effects. J Endocrinol Invest. 2016;39:983–90. doi: 10.1007/s40618-016-0467-z.
    1. Lokkegaard E, Jovanovic Z, Heitmann BL, Keiding N, Ottesen B, Pedersen AT. The association between early menopause and risk of ischaemic heart disease: influence of hormone therapy. Maturitas. 2006;53:226–33. doi: 10.1016/j.maturitas.2005.04.009.
    1. Vujovic S. Aetiology of premature ovarian failure. Menopause Int. 2009;15:72–5.
    1. Alexander RP, Fang G, Rozowsky J, Snyder M, Gerstein MB. Annotating non-coding regions of the genome. Nat Rev Genet. 2010;11:559–71. doi: 10.1038/nrg2814.
    1. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004;5:522–31. doi: 10.1038/nrg1379.
    1. Mendell JT. MicroRNAs: critical regulators of development, cellular physiology and malignancy. Cell Cycle. 2005;4:1179–84. doi: 10.4161/cc.4.9.2032.
    1. Esteller M. Non-coding RNAs in human disease. Nat Rev Genet. 2011;12:861–74. doi: 10.1038/nrg3074.
    1. Krol J, Loedige I, Filipowicz W. The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet. 2010;11:597–610.
    1. Li Y, Fang Y, Liu Y, Yang X. MicroRNAs in ovarian function and disorders. J Ovarian Res. 2015;8:51. doi: 10.1186/s13048-015-0162-2.
    1. Maalouf SW, Liu WS, Pate JL. MicroRNA in ovarian function. Cell Tissue Res. 2016;363:7–18. doi: 10.1007/s00441-015-2307-4.
    1. Imbar T, Eisenberg I. Regulatory role of microRNAs in ovarian function. Fertil Steril. 2014;101:1524–30. doi: 10.1016/j.fertnstert.2014.04.024.
    1. van Noord PA, Dubas JS, Dorland M, Boersma H, te Velde E. Age at natural menopause in a population-based screening cohort: the role of menarche, fecundity, and lifestyle factors. Fertil Steril. 1997;68:95–102. doi: 10.1016/S0015-0282(97)81482-3.
    1. Coulam CB, Adamson SC, Annegers JF. Incidence of premature ovarian failure. Obstet Gynecol. 1986;67:604–6.
    1. Jiao X, Qin C, Li J, Qin Y, Gao X, Zhang B, Zhen X, Feng Y, Simpson JL, Chen ZJ. Cytogenetic analysis of 531 Chinese women with premature ovarian failure. Hum Reprod. 2012;27:2201–7. doi: 10.1093/humrep/des104.
    1. Bidet M, Bachelot A, Bissauge E, Golmard JL, Gricourt S, Dulon J, Coussieu C, Badachi Y, Touraine P. Resumption of ovarian function and pregnancies in 358 patients with premature ovarian failure. J Clin Endocrinol Metab. 2011;96:3864–72. doi: 10.1210/jc.2011-1038.
    1. Sassarini J, Lumsden MA, Critchley HO. Sex hormone replacement in ovarian failure - new treatment concepts. Best Pract Res Clin Endocrinol Metab. 2015;29:105–14. doi: 10.1016/j.beem.2014.09.010.
    1. Pacello PC, Yela DA, Rabelo S, Giraldo PC, Benetti-Pinto CL. Dyspareunia and lubrication in premature ovarian failure using hormonal therapy and vaginal health. Climacteric. 2014;17:342–7. doi: 10.3109/13697137.2013.860116.
    1. Uygur D, Sengul O, Bayar D, Erdinc S, Batioglu S, Mollamahmutoglu L. Bone loss in young women with premature ovarian failure. Arch Gynecol Obstet. 2005;273:17–9. doi: 10.1007/s00404-005-0029-7.
    1. Popat VB, Calis KA, Vanderhoof VH, Cizza G, Reynolds JC, Sebring N, Troendle JF, Nelson LM. Bone mineral density in estrogen-deficient young women. J Clin Endocrinol Metab. 2009;94:2277–83. doi: 10.1210/jc.2008-1878.
    1. Nelson LM, Covington SN, Rebar RW. An update: spontaneous premature ovarian failure is not an early menopause. Fertil Steril. 2005;83:1327–32. doi: 10.1016/j.fertnstert.2004.11.059.
    1. Leite-Silva P, Bedone A, Pinto-Neto AM, Costa JV, Costa-Paiva L. Factors associated with bone density in young women with karyotypically normal spontaneous premature ovarian failure. Arch Gynecol Obstet. 2009;280:177–81. doi: 10.1007/s00404-008-0881-3.
    1. Bakhsh H, Dei M, Bucciantini S, Balzi D, Bruni V. Premature ovarian insufficiency in young girls: repercussions on uterine volume and bone mineral density. Gynecol Endocrinol. 2015;31:65–9. doi: 10.3109/09513590.2014.958987.
    1. van Der Voort DJ, van Der Weijer PH, Barentsen R. Early menopause: increased fracture risk at older age. Osteoporos Int. 2003;14:525–30. doi: 10.1007/s00198-003-1408-1.
    1. Jacobsen BK, Knutsen SF, Fraser GE. Age at natural menopause and total mortality and mortality from ischemic heart disease: the Adventist Health Study. J Clin Epidemiol. 1999;52:303–7. doi: 10.1016/S0895-4356(98)00170-X.
    1. Phung TK, Waltoft BL, Laursen TM, Settnes A, Kessing LV, Mortensen PB, Waldemar G. Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Dement Geriatr Cogn Disord. 2010;30:43–50. doi: 10.1159/000314681.
    1. Nappi RE, Sinforiani E, Mauri M, Bono G, Polatti F, Nappi G. Memory functioning at menopause: impact of age in ovariectomized women. Gynecol Obstet Invest. 1999;47:29–36. doi: 10.1159/000010058.
    1. Bove R, Secor E, Chibnik LB, Barnes LL, Schneider JA, Bennett DA, De Jager PL. Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2014;82:222–9. doi: 10.1212/WNL.0000000000000033.
    1. Farrag AK, Khedr EM, Abdel-Aleem H, Rageh TA. Effect of surgical menopause on cognitive functions. Dement Geriatr Cogn Disord. 2002;13:193–8. doi: 10.1159/000048652.
    1. Rocca WA, Shuster LT, Grossardt BR, Maraganore DM, Gostout BS, Geda YE, Melton LJ., 3rd Long-term effects of bilateral oophorectomy on brain aging: unanswered questions from the Mayo Clinic Cohort Study of Oophorectomy and Aging. Womens Health (Lond) 2009;5:39–48. doi: 10.2217/17455057.5.1.39.
    1. Hirshfeld-Cytron J, Gracia C, Woodruff TK. Nonmalignant diseases and treatments associated with primary ovarian failure: an expanded role for fertility preservation. J Womens Health (Larchmt) 2011;20:1467–77. doi: 10.1089/jwh.2010.2625.
    1. Qin Y, Jiao X, Simpson JL, Chen ZJ. Genetics of primary ovarian insufficiency: new developments and opportunities. Hum Reprod Update. 2015;21:787–808. doi: 10.1093/humupd/dmv036.
    1. Vujovic S, Ivovic M, Tancic-Gajic M, Marina L, Barac M, Arizanovic Z, Nenezic A, Ivanisevic M, Micic J, Sajic S, Micic D. Premature ovarian failure. Srp Arh Celok Lek. 2012;140:806–11. doi: 10.2298/SARH1212806V.
    1. Mattick JS, Makunin IV. Non-coding RNA. Hum Mol Genet. 2006;15(Spec No 1):R17–29. doi: 10.1093/hmg/ddl046.
    1. Bernstein E, Kim SY, Carmell MA, Murchison EP, Alcorn H, Li MZ, Mills AA, Elledge SJ, Anderson KV, Hannon GJ. Dicer is essential for mouse development. Nat Genet. 2003;35:215–7. doi: 10.1038/ng1253.
    1. Yuan SQ, Ortogero N, Wu QX, Zheng HL, Yan W. Murine follicular development requires oocyte DICER, but Not DROSHA. Biol Reprod. 2014;91:39. doi: 10.1095/biolreprod.114.119370.
    1. Mattiske DM, Han L, Mann JR. Meiotic maturation failure induced by DICER1 deficiency is derived from primary oocyte ooplasm. Reproduction. 2009;137:625–32. doi: 10.1530/REP-08-0475.
    1. Murchison EP, Stein P, Xuan Z, Pan H, Zhang MQ, Schultz RM, Hannon GJ. Critical roles for Dicer in the female germline. Genes Dev. 2007;21:682–93. doi: 10.1101/gad.1521307.
    1. Rah H, Jeon YJ, Lee BE, Kim JO, Shim SH, Lee WS, Choi DH, Kim JH, Kim NK. Association of polymorphisms in microRNA machinery genes (DROSHA, DICER1, RAN, and XPO5) with risk of idiopathic primary ovarian insufficiency in Korean women. Menopause. 2013;20:1067–73. doi: 10.1097/GME.0b013e3182883907.
    1. Yang X, Zhou Y, Peng S, Wu L, Lin HY, Wang S, Wang H. Differentially expressed plasma microRNAs in premature ovarian failure patients and the potential regulatory function of mir-23a in granulosa cell apoptosis. Reproduction. 2012;144:235–44. doi: 10.1530/REP-11-0371.
    1. Dang Y, Zhao S, Qin Y, Han T, Li W, Chen ZJ. MicroRNA-22-3p is down-regulated in the plasma of Han Chinese patients with premature ovarian failure. Fertil Steril. 2015;103:802–7. doi: 10.1016/j.fertnstert.2014.12.106.
    1. Chhabra R, Dubey R, Saini N. Cooperative and individualistic functions of the microRNAs in the miR-23a ~ 27a ~ 24-2 cluster and its implication in human diseases. Mol Cancer. 2010;9:232. doi: 10.1186/1476-4598-9-232.
    1. Huang S, He X, Ding J, Liang L, Zhao Y, Zhang Z, Yao X, Pan Z, Zhang P, Li J, et al. Upregulation of miR-23a approximately 27a approximately 24 decreases transforming growth factor-beta-induced tumor-suppressive activities in human hepatocellular carcinoma cells. Int J Cancer. 2008;123:972–8. doi: 10.1002/ijc.23580.
    1. Nie M, Yu S, Peng S, Fang Y, Wang H, Yang X. miR-23a and miR-27a promote human granulosa cell apoptosis by targeting SMAD5. Biol Reprod. 2015;93:98. doi: 10.1095/biolreprod.115.130690.
    1. Kim YJ, Ku SY, Kim YY, Liu HC, Chi SW, Kim SH, Choi YM, Kim JG, Moon SY. MicroRNAs transfected into granulosa cells may regulate oocyte meiotic competence during in vitro maturation of mouse follicles. Hum Reprod. 2013;28:3050–61. doi: 10.1093/humrep/det338.
    1. Armstrong DG, McEvoy TG, Baxter G, Robinson JJ, Hogg CO, Woad KJ, Webb R, Sinclair KD. Effect of dietary energy and protein on bovine follicular dynamics and embryo production in vitro: associations with the ovarian insulin-like growth factor system. Biol Reprod. 2001;64:1624–32. doi: 10.1095/biolreprod64.6.1624.
    1. Spicer LJ. Proteolytic degradation of insulin-like growth factor binding proteins by ovarian follicles: a control mechanism for selection of dominant follicles. Biol Reprod. 2004;70:1223–30. doi: 10.1095/biolreprod.103.021006.
    1. Xiong J, Yu D, Wei N, Fu H, Cai T, Huang Y, Wu C, Zheng X, Du Q, Lin D, Liang Z. An estrogen receptor alpha suppressor, microRNA-22, is downregulated in estrogen receptor alpha-positive human breast cancer cell lines and clinical samples. FEBS J. 2010;277:1684–94. doi: 10.1111/j.1742-4658.2010.07594.x.
    1. Rah H, Jeon YJ, Shim SH, Cha SH, Choi DH, Kwon H, Kim JH, Shin JE, Kim NK. Association of miR-146aC > G, miR-196a2T > C, and miR-499A > G polymorphisms with risk of premature ovarian failure in Korean women. Reprod Sci. 2013;20:60–8. doi: 10.1177/1933719112450341.
    1. Chen X, Xie M, Liu D, Shi K. Downregulation of microRNA146a inhibits ovarian granulosa cell apoptosis by simultaneously targeting interleukin1 receptorassociated kinase and tumor necrosis factor receptorassociated factor 6. Mol Med Rep. 2015;12:5155–62.
    1. de los Santos Jose M, Anderson DJ, Racowsky C, Hill JA. Presence of Fas-Fas ligand system and bcl-2 gene products in cells and fluids from gonadotropin-stimulated human ovaries. Biol Reprod. 2000;63:1811–1816. doi: 10.1095/biolreprod63.6.1811.
    1. Abd El Naby WS, Hagos TH, Hossain MM, Salilew-Wondim D, Gad AY, Rings F, Cinar MU, Tholen E, Looft C, Schellander K, et al. Expression analysis of regulatory microRNAs in bovine cumulus oocyte complex and preimplantation embryos. Zygote. 2013;21:31–51. doi: 10.1017/S0967199411000566.
    1. Suzuki Y, Kim HW, Ashraf M, Haider H. Diazoxide potentiates mesenchymal stem cell survival via NF-kappaB-dependent miR-146a expression by targeting Fas. Am J Physiol Heart Circ Physiol. 2010;299:H1077–82. doi: 10.1152/ajpheart.00212.2010.
    1. Hussein MR. Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update. 2005;11:162–77. doi: 10.1093/humupd/dmi001.
    1. Tripurani SK, Lee KB, Wee G, Smith GW, Yao J. MicroRNA-196a regulates bovine newborn ovary homeobox gene (NOBOX) expression during early embryogenesis. BMC Dev Biol. 2011;11:25. doi: 10.1186/1471-213X-11-25.
    1. Qin Y, Choi Y, Zhao H, Simpson JL, Chen ZJ, Rajkovic A. NOBOX homeobox mutation causes premature ovarian failure. Am J Hum Genet. 2007;81:576–81. doi: 10.1086/519496.
    1. Medeiros LA, Dennis LM, Gill ME, Houbaviy H, Markoulaki S, Fu D, White AC, Kirak O, Sharp PA, Page DC, Jaenisch R. Mir-290-295 deficiency in mice results in partially penetrant embryonic lethality and germ cell defects. Proc Natl Acad Sci U S A. 2011;108:14163–8. doi: 10.1073/pnas.1111241108.
    1. Rah H, Kim HS, Cha SH, Kim YR, Lee WS, Ko JJ, Kim NK. Association of breast cancer-related microRNA polymorphisms with idiopathic primary ovarian insufficiency. Menopause. 2015;22:437–43. doi: 10.1097/GME.0000000000000325.
    1. Xiao GY, Cheng CC, Chiang YS, Cheng WT, Liu IH, Wu SC. Exosomal miR-10a derived from amniotic fluid stem cells preserves ovarian follicles after chemotherapy. Sci Rep. 2016;6:23120. doi: 10.1038/srep23120.
    1. Yamamoto Y, Kosaka N, Tanaka M, Koizumi F, Kanai Y, Mizutani T, Murakami Y, Kuroda M, Miyajima A, Kato T, Ochiya T. MicroRNA-500 as a potential diagnostic marker for hepatocellular carcinoma. Biomarkers. 2009;14:529–38. doi: 10.3109/13547500903150771.
    1. Zheng GXY, Ravi A, Calabrese JM, Medeiros LA, Kirak O, Dennis LM, Jaenisch R, Burge CB, Sharp PA. A latent pro-survival function for the mir-290-295 cluster in mouse embryonic stem cells. PLoS Genet. 2011;7:e1002054. doi: 10.1371/journal.pgen.1002054.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅