Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan, USA.
Department of Physiology, Michigan State University, East Lansing, Michigan, USA.
J Endocrinol. 2021 Jun;249(3):R53-R64. doi: 10.1530/JOE-20-0578.
In recent years, androgens have emerged as critical regulators of female reproduction and women's health in general. While high levels of androgens in women are associated with polycystic ovary syndrome (PCOS), recent evidence suggests that a certain amount of direct androgen action through androgen receptor is also essential for normal ovarian function. Moreover, prenatal androgen exposure has been reported to cause developmental reprogramming of the fetus that manifests into adult pathologies, supporting the Developmental Origins of Health and Disease (DOHaD) hypothesis. Therefore, it has become imperative to understand the underlying mechanism of androgen actions and its downstream effects under normal and pathophysiological conditions. Over the years, there has been a lot of studies on androgen receptor function as a transcriptional regulator in the nucleus as well as androgen-induced rapid extra-nuclear signaling. Conversely, new evidence suggests that androgen actions may also be mediated through epigenetic modulation involving both the nuclear and extra-nuclear androgen signaling. This review focuses on androgen-induced epigenetic modifications in female reproduction, specifically in the ovary, and discusses emerging concepts, latest perceptions, and highlight the areas that need further investigation.
近年来,雄激素已成为女性生殖和整体健康的关键调节因子。虽然高水平的女性雄激素与多囊卵巢综合征(PCOS)有关,但最近的证据表明,通过雄激素受体的一定量的直接雄激素作用对于正常卵巢功能也是必不可少的。此外,据报道,产前雄激素暴露会导致胎儿的发育重编程,表现为成年期病理,支持健康与疾病的发育起源(DOHaD)假说。因此,了解雄激素作用的潜在机制及其在正常和病理生理条件下的下游效应变得至关重要。多年来,人们对雄激素受体在核内作为转录调节剂的功能以及雄激素诱导的快速核外信号转导进行了大量研究。相反,新的证据表明,雄激素作用也可能通过涉及核内和核外雄激素信号的表观遗传调节来介导。这篇综述重点介绍了雄激素诱导的女性生殖,特别是卵巢中的表观遗传修饰,并讨论了新兴概念、最新认识,并强调了需要进一步研究的领域。