Acknowledgment
We thank Suzanne M. Moenter, PhD, for her comments on an earlier draft of this manuscript.
Funding Source
This work was funded, in part, by NIH grants P50 HD028934 (PI: Marshall), P50 HD044405 (PI: Dunaif), and P50 HD071836 (PI: Stouffer).
Disclosure Statement
The authors declare that they have no potential conflicts of interest to disclose.
References
1Escobar-Morreale HF: Polycystic ovary syndrome: definition, aetiology, diagnosis and treatment. Nat Rev Endocrinol 2018;14:270–284.
2Foecking EM, McDevitt MA, Acosta-Martínez M, Horton TH, Levine JE: Neuroendocrine consequences of androgen excess in female rodents. Horm Behav 2008;53:673–692.
3Moore AM, Campbell RE: Polycystic ovary syndrome: understanding the role of the brain. Front Neuroendocrinol 2017;46:1–14.
4Burt Solorzano CM, Beller JP, Abshire MY, Collins JS, McCartney CR, Marshall JC: Neuroendocrine dysfunction in polycystic ovary syndrome. Steroids 2012;77:332–337.
5Lie Fong S, Laven JSE, Duhamel A, Dewailly D: Polycystic ovarian morphology and the diagnosis of polycystic ovary syndrome: redefining threshold levels for follicle count and serum anti-Müllerian hormone using cluster analysis. Hum Reprod 2017;32:1723–1731.
6Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, Lobo R, Norman RJ, Talbott E, Dumesic DA: Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010;95:2038–2049.
7Nasiri Amiri F, Ramezani Tehrani F, Esmailzadeh S, Tohidi M, Azizi F, Basirat Z: Sexual function in women with polycystic ovary syndrome and their hormonal and clinical correlations. Int J Impot Res 2018;30:54-61.
8Teede HJ, Joham AE, Paul E, Moran LJ, Loxton D, Jolley D, Lombard C: Longitudinal weight gain in women identified with polycystic ovary syndrome: results of an observational study in young women. Obesity (Silver Spring) 2013;21:1526–1532.
9Abbott DH, Dumesic DA, Eisner JR, Kemnitz JW, Goy RW: The prenatally androgenized female rhesus monkey as a model for polycystic ovarian syndrome; in Azziz R, Nestler JE, Dewailly D (eds): Androgen Excess Disorders in Women. Philadelphia, Lippencott-Raven Press, 1997, pp 369–382.
10Dumesic DA, Abbott DH, Eisner JR, Goy RW: Prenatal exposure of female rhesus monkeys to testosterone propionate increases serum luteinizing hormone levels in adulthood. Fertil Steril 1997;67:155–163.
11Xu N, Kwon S, Abbott DH, Geller DH, Dumesic DA, Azziz R, Guo X, Goodarzi MO: Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. PLoS One 2011;6:e27286.
12Abbott DH, Levine JE, Dumesic DA: Translational insight into polycystic ovary syndrome (PCOS) from female monkeys with PCOS-like traits. Curr Pharm Des 2016;22:5625–5633.
13West C, Foster DL, Evans NP, Robinson J, Padmanabhan V: Intra-follicular activin availability is altered in prenatally-androgenized lambs. Mol Cell Endocrinol 2001;185:51–59.
14Sullivan SD, Moenter SM: Prenatal androgens alter GABAergic drive to gonadotropin-releasing hormone neurons: implications for a common fertility disorder. Proc Natl Acad Sci USA 2004;101:7129–7134.
15Foecking EM, Szabo M, Schwartz NB, Levine JE: Neuroendocrine consequences of prenatal androgen exposure in the female rat: absence of luteinizing hormone surges, suppression of progesterone receptor gene expression, and acceleration of the gonadotropin-releasing hormone pulse generator. Biol Reprod 2005;72:1475–1483.
16Padmanabhan V, Cardoso RC, Puttabyatappa M: Developmental programming, a pathway to disease. Endocrinology 2016;157:1328–1340.
17Walters KA: Androgens in polycystic ovary syndrome: lessons from experimental models. Curr Opin Endocrinol Diabetes Obes 2016;23:257–263.
18Moore AM, Campbell RE: Polycystic ovary syndrome: understanding the role of the brain. Front Neuroendocrinol 2017;46:1–14.
19de Zegher F, Ibáñez L: Early Origins of polycystic ovary syndrome: hypotheses may change without notice. J Clin Endocrinol Metab 2009;94:3682–3685.
20Filippou P, Homburg R: Is foetal hyperexposure to androgens a cause of PCOS? Hum Reprod Update 2017;23:421–432.
21Beck-Peccoz P, Padmanabhan V, Baggiani AM, Cortelazzi D, Buscaglia M, Medri G, Marconi AM, Pardi G, Beitins IZ: Maturation of hypothalamic-pituitary-gonadal function in normal human fetuses: circulating levels of gonadotropins, their common alpha-subunit and free testosterone, and discrepancy between immunological and biological activities of circulating follicle-stimulating hormone. J Clin Endocrinol Metab 1991;73:525–532.
22Abbott DH, Barnett DK, Levine JE, Padmanabhan V, Dumesic DA, Jacoris S, Tarantal AF: Endocrine antecedents of polycystic ovary syndrome in fetal and infant prenatally androgenized female rhesus monkeys. Biol Reprod 2008;79:154–163.
23Veiga-Lopez A, Steckler TL, Abbott DH, Welch KB, MohanKumar PS, Phillips DJ, Refsal K, Padmanabhan V: Developmental programming: impact of excess prenatal testosterone on intrauterine fetal endocrine milieu and growth in sheep. Biol Reprod 2011;84:87–96.
24Palomba S, Marotta R, Di Cello A, Russo T, Falbo A, Orio F, Tolino A, Zullo F, Esposito R, La Sala GB: Pervasive developmental disorders in children of hyperandrogenic women with polycystic ovary syndrome: a longitudinal case-control study. Clin Endocrinol (Oxf) 2012;77:898–904.
