Contributions of androgen and estrogen to fetal programming of ovarian dysfunction.
In female mammals, including humans, deviations from normal androgenic or estrogenic exposure during fetal development are detrimental to subsequent adult ovarian function. Androgen deficiency, without accompanying estrogen deficit, has little apparent impact on ovarian development. Fetal estrogen deficiency, on the other hand, results in impaired oocyte and follicle development, immature and abnormal adult ovaries, and excessive ovarian stimulation from endogenous gonadotropins ultimately generating hemorrhagic follicles. Complete estrogen deficiency lasting into adulthood results in partial ovarian masculinization. Fetal androgen excess, on the other hand, mediated either by direct androgen action or following androgen aromatization to estrogen, reprograms ovarian development and reproductive neuroendocrinology to mimic that found in women with polycystic ovary syndrome: enlarged, polyfollicular, hyperandrogenic, anovulatory ovaries with accompanying LH hypersecretion. Oocyte developmental competence is also compromised. Insulin is implicated in the mechanism of both anovulation and deficient oocyte development. Fetal estrogen excess induces somewhat similar disruption of adult ovarian function to fetal androgen excess. Understanding the quality of the fetal female sex steroid hormone environment is thus becoming increasingly important in improving our knowledge of mechanisms underlying a variety of female reproductive pathologies.
Abbott
David H
DH
National Primate Research Center, Department of Ob/Gyn, Endocrinology-Reproductive Physiology Training Program, University of Wisconsin, Madison, WI 53715, USA. abbott@primate.wisc.edu
Padmanabhan
Vasantha
V
Dumesic
Daniel A
DA
D000728:Androgens / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D004967:Estrogens / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D005260:Female; D047109:Fetal Development; D006801:Humans; D008954:Models, Biological; D010049:Ovarian Diseases / Q000196:embryology* / Q000235:genetics / Q000378:metabolism; D010053:Ovary / Q000196:embryology* / Q000378:metabolism / Q000503:physiopathology
D000728:Androgens; D004967:Estrogens