Contributions of androgen and estrogen to fetal programming of ovarian dysfunction

Abstract

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.

Neonatal Exposure to Agonists and Antagonists of Sex Steroid Receptors Affects AMH and FSH Plasma Level and Their Receptors Expression in the Adult Pig Ovary

“…In addition, in small antral follicles, neonatal OP or ICI treatment resulted in decreased AMH expression, while it was increased in response to neonatal TP and FLU treatment. Abbott et al [29] summarized the effect of estrogen excess or deficiency on ovarian function in adulthood, suggesting that fetal exposure to chemicals derived from environment or diet binding to estrogen receptors may cause reprogramming of ovarian function in adulthood. In addition, we have previously demonstrated that neonatal exposure to antiandrogenic and estrogenic compounds altered GDF9 and BMP15 signalling networks within the antral follicle and may disturb the follicular steroidogenesis and readiness to further growth [11].…”

Male twins reduce fitness of female co-twins in humans

“…Studies in humans and other mammals show that the more feminine females are preferred as mates by males (9,35,36), and direct evidence from laboratory animals confirms that intrauterine position can affect female attractiveness to males (37,38). Second, exposure to male co-twins reduces female fecundity, possibly because elevated levels of testosterone during development promote the onset of diseases that compromise fertility, such as polycystic ovary syndrome (39,40) and reproductive cancers (41,42).…”

Steroidogenic versus Metabolic Programming of Reproductive Neuroendocrine, Ovarian and Metabolic Dysfunctions

“…Androgens and estrogens play an important role in the development of the brain [21, 22] and establishment of neuroendocrine feedback mechanisms controlling gonadotropin-releasing hormone (GnRH) and gonadotropin release [17]. Steroid hormones also act directly at the pituitary levels regulating synthesis and secretion of gonadotropins [23, 24], and at the ovarian level controlling folliculogenesis and steroidogenesis [25, 26]. Thus, improper developmental steroid exposure mediates the programming of adult reproductive disorders in prenatal T-treated females.…”