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Chapter 7 - Origins of Polycystic Ovary Syndrome In Utero

Published online by Cambridge University Press:  13 May 2022

By
Roy Homburg  and
Claudia Raperport
Edited by
Gabor T. Kovacs ,
Bart Fauser  and
Richard S. Legro
Gabor T. Kovacs
Affiliation:
Monash University, Melbourne, Australia
Bart Fauser
Affiliation:
University Medical Center, Utrecht, Netherlands
Richard S. Legro
Affiliation:
Penn State Medical Center, Hershey, PA, USA
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Summary

Polycystic ovarian syndrome (PCOS) affects up to 18% of women internationally, with widespread effects on their reproductive, metabolic and cardiovascular health. To date, the etiology of this syndrome remains unclear. Patterns of expression within family groups suggest a genetic inheritance but neither a clear inheritance pattern nor candidate gene(s) has been discovered to date. Animal studies have proven that in utero exposure to high levels of androgen can elicit PCOS-like traits in various mammals, including rhesus monkeys who share a similar reproductive biology with humans. An alternate mechanism for etiology is the epigenetic alteration in programming of the fetal ovaries in response to androgen exposure. This chapter summarizes the evidence available and hypothesizes possible mechanisms of action via which PCOS could be transmitted from an affected mother to her offspring. The origins of androgens in the fetal circulation as well as the role of AMH and luteinizing hormone (LH) are discussed as are the actions of the placenta and the difference in placental function and hormone secretion patterns in PCOS females compared to “normal” physiology.

Keywords

polycystic ovarian syndrome (PCOS)epigeneticandrogenin uteroplacentaanti-Müllerian hormone (AMH)familialBarker hypothesis
Type
Chapter
Information
Polycystic Ovary Syndrome , pp. 58 - 66
Publisher: Cambridge University Press
Print publication year: 2022

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References

Stein, I. and Leventhal, M. Amenorrhoea associated with bilateral polycystic ovaries. Am J Obstet Gynecol 1935; 29: 181–191.Google Scholar
Diamanti-Kandarakis, E. and Panidis, D. Unravelling the phenotypic map of polycystic ovary syndrome (PCOS): A prospective study of 634 women with PCOS. Clin Endocrinol (Oxf) 2007; 67(5): 735–742.Google Scholar
Rotterdam Consensus Consensus on women’s health aspects of polycystic ovary syndrome (PCOS). Hum Reprod 2012; 27(1): 14–24.CrossRefGoogle Scholar
Kahsar-Miller, M. D. Prevalence of polycystic ovary syndrome (PCOS) in first degree relatives of patients with PCOS. Fertil Steril 2001; 75(1): 53–58.Google Scholar
Legro, R. S., Driscoll, D., Strauss, J. F., III, Fox, J. and Dunaif, A. Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci USA 1998; 95(25): 14956–14960.CrossRefGoogle ScholarPubMed
Govind, A., Obhrai, M. S. and Clayton, R. N. Polycystic ovaries are inherited as an autosomal dominant trait: Analysis of 29 polycystic ovary syndrome and 10 control families. J Clin Endocrinol Metab 1999; 84(1): 38–43.Google Scholar
Carey, A. H., Chan, K. L., Short, F., White, D., Williamson, R. and Franks, S. Evidence for a single gene effect causing polycystic ovaries and male pattern baldness. Clin Endocrinol 1993; 38(6): 653–658.CrossRefGoogle ScholarPubMed
Jahanfar, S., Eden, J. A., Warren, P., Seppälä, M. and Nguyen, T. V. A twin study of polycystic ovary syndrome. Fertil Steril 1995; 63(3): 478–486.Google Scholar
Vink, J. M., Sadrzadeh, S., Lambalk, C. B., and Boomsma, D. I. Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 2006; 91(6): 2100–2104.Google Scholar
Day, F., Karaderi, T., Jones, M. R. et al. Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria. PLoS Genetics 2018; 14(12): e1007813.CrossRefGoogle ScholarPubMed
Dapas, M., Lin, F. T. J., Nadkarni, G. N. et al. Distinct subtypes of polycystic ovary syndrome with novel genetic associations: An unsupervised, phenotypic clustering analysis. 2020; PLoS Med 17(6): e1003132.Google Scholar
Ehrmann, D. A., Liljenquist, D. R., Kasza, K., Azziz, R., Legro, R. S. and Ghazzi, M. N. Prevalence and predictors of the metabolic syndrome in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91(1): 48–53.Google Scholar
Lo, J. C., Feigenbaum, S. L., Yang, J., Pressman, A. R., Selby, J. V. and Go, A. S. Epidemiology and adverse cardiovascular risk profile of diagnosed polycystic ovary syndrome. J Clin Endocrinol Metab 2006; 91(4): 1357–1363.Google Scholar
Casarini, L. and Brigante, G. The polycystic ovary syndrome evolutionary paradox: A genome-wide association studies-based, in silico, evolutionary explanation. J Clin Endocrinol Metab 2014; 99(11): E2412–2420.Google Scholar
Deligeoroglou, E., Kouskouti, C. and Christopoulos, P. The role of genes in the polycystic ovary syndrome: Predisposition and mechanisms. Gynecol Endocrinol 2009; 25(9): 603–609.CrossRefGoogle ScholarPubMed
Barker, D. J. The developmental origins of adult disease. J Am Coll Nutr 2004; 23(6 Suppl): 588s–595s.Google Scholar
Rittmaster, R. S. Antiandrogen treatment of polycystic ovary syndrome. Endocrinol Metab Clin North Am 1999; 28(2): 409–421.Google Scholar
Fels, E. and Bosch, L. R. Effect of prenatal administration of testosterone on ovarian function in rats. Am J Obstet Gynecol 1971; 111(7): 964–969.Google Scholar
Parker, C. R., Jr. and Mahesh, V. B. Interrelationship between excessive levels of circulating androgens in blood and ovulatory failure. J Reprod Med 1976; 17(2): 75–90.Google Scholar
Padmanabhan, V. and Veiga-Lopez, A. Sheep models of polycystic ovary syndrome phenotype. Mol Cell Endocrinol 2013; 373(1–2): 8–20.Google Scholar
Clarke, I. J., Scaramuzzi, R. J. and Short, R. V. Ovulation in prenatally androgenized ewes. J Endocrinol 1977; 73(2): 385–389.Google Scholar
Forsdike, R. A., Hardy, K., Bull, L. et al. Disordered follicle development in ovaries of prenatally androgenized ewes. J Endocrinol 2007; 192(2): 421–428.Google Scholar
Smith, P., Steckler, T. L., Veiga-Lopez, A. and Padmanabhan, V. Developmental programming: Differential effects of prenatal testosterone and dihydrotestosterone on follicular recruitment, depletion of follicular reserve, and ovarian morphology in sheep. Biol Reprod 2009; 80(4): 726–736.Google Scholar
Recabarren, S. E., Padmanabhan, V., Codner, E. et al. Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone. Am J Physiol Endocrinol Metab 2005; 289(5): E801-806.Google Scholar
Steckler, T. L., Roberts, E. K., Doop, D. D., Lee, T. M. and Padmanabhan, V. Developmental programming in sheep: Administration of testosterone during 60–90 days of pregnancy reduces breeding success and pregnancy outcome. Theriogenology 2007; 67(3): 459–467.Google Scholar
Xu, N., Kwon, S., Abbott, D. H. et al. Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. PLoS One 2011; 6(11): e27286.Google Scholar
Amalfi, S., Velez, L. M., Heber, M. F. et al. Prenatal hyperandrogenization induces metabolic and endocrine alterations which depend on the levels of testosterone exposure. PLoS One 2012; 7(5): e37658.CrossRefGoogle ScholarPubMed
Crisosto, N., Echiburú, B., Maliqueo, M. et al. Improvement of hyperandrogenism and hyperinsulinemia during pregnancy in women with polycystic ovary syndrome: Possible effect in the ovarian follicular mass of their daughters. Fertil Steril 2012; 97(1): 218–224.CrossRefGoogle ScholarPubMed
Dumesic, D. A. and Richards, J. S. Ontogeny of the ovary in polycystic ovary syndrome. Fertil Steril 2013; 100(1): 23–38.Google Scholar
Yildiz, B. O. and Azziz, R. The adrenal and polycystic ovary syndrome. Rev Endocr Metab Disord 2007; 8(4): 331–342.CrossRefGoogle ScholarPubMed
Homburg, R. and Crawford, G. The role of AMH in anovulation associated with PCOS: A hypothesis. Hum Reprod 2014; 29(6): 1117–1121.Google Scholar
Lambertini, L., Saul, S. R., Copperman, A. B. et al. Intrauterine reprogramming of the polycystic ovary syndrome: Evidence from a pilot study of cord blood global methylation analysis. Front Endocrinol (Lausanne) 2017; 8: 352.CrossRefGoogle ScholarPubMed
Abbott, D. H., Barnett, D. K., Levine, J. E. et al. Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod 2008; 79(1): 154–163.CrossRefGoogle ScholarPubMed
Maliqueo, M., Lara, H. E., Sánchez, F., Echiburú, B., Crisosto, N. and Sir-Petermann, T. Placental steroidogenesis in pregnant women with polycystic ovary syndrome. Eur J Obstet Gynecol Reprod Biol 2013; 166(2): 151–155.Google Scholar
Catteau-Jonard, S., Jamin, S. P., Leclerc, A., Gonzalès, J., Dewailly, D. and di Clemente, N. Anti-Mullerian hormone, its receptor, FSH receptor, and androgen receptor genes are overexpressed by granulosa cells from stimulated follicles in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2008; 93(11): 4456–4461.Google Scholar
Tata, B., Mimouni, N. E. H., Barbotin, A. L. et al. Elevated prenatal anti-Müllerian hormone reprograms the fetus and induces polycystic ovary syndrome in adulthood. Nat Med 2018; 24(6): 834–846.CrossRefGoogle ScholarPubMed
Rajpert-De Meyts, E., Jørgensen, N., Graem, N., Müller, J., Cate, R. L. and Skakkebaek, N. E. Expression of anti-Müllerian hormone during normal and pathological gonadal development: Association with differentiation of Sertoli and granulosa cells. J Clin Endocrinol Metab 1999; 84(10): 3836–3844.Google Scholar
Homburg, R., Gudi, A., Shah, A. and Layton, A. M. A novel method to demonstrate that pregnant women with polycystic ovary syndrome hyper-expose their fetus to androgens as a possible stepping stone for the developmental theory of PCOS: A pilot study. Reprod Biol Endocrinol 2017; 15(1): 61–65.Google Scholar

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