EFFECTS OF ANDROGENS ON OVARIAN STRUCTURE AND FUNCTION

雄激素对雌性性别分化的影响通常在病理背景下被认为（例如，先天性肾上腺增生导致的模糊生殖器），但在斑点鬣狗中，胎儿发育和性别分化期间的高雄激素环境代表正常生理，而不是病理。因此，斑点鬣狗代表了一个独特的系统，研究产前雄激素对性别分化的影响。在子宫内暴露于高雄激素会使雌性外生殖器男性化到极点，但雄激素对卵巢分化的影响尚未得到很好的研究。具体来说，雄激素似乎增加了发育中的卵巢的卵泡闭锁率，这可能解释了斑点鬣狗卵巢间质组织丰富而卵泡相对较少的原因。在拟议的研究中，我将研究一组雌性鬣狗，这些鬣狗以前在子宫内接触过抗雄激素。这些女性现在已经成年，她们的卵巢结构和功能将与未治疗的对照组进行比较。体内和体外（单侧卵巢切除术后）将评估卵巢对促性腺激素激发试验的类固醇性反应。卵巢切除术后，将测量卵泡数量和类固醇生成酶活性，并通过免疫细胞化学定量类固醇受体水平。这项研究将提高我们对产前暴露于雄激素如何影响卵巢结构和功能的理解。

Effects of androgens on female sexual differentiation are often considered within a pathological context (e.g. ambiguous genitalia resulting from congenital adrenal hyperplasia), but in the spotted hyena a high androgen milieu during fetal development and sexual differentiation represents normal physiology, not pathology. Thus, the spotted hyena represents a unique system in which to study the effects of antenatal androgens on sexual differentiation. High androgen exposure in utero masculinizes female external genitalia to the extreme in spotted hyenas, but the effects of androgens on ovarian differentiation are not well studied. Specifically, androgens appear to increase the rate of follicular atresia in the developing ovary, which may explain the abundance of ovarian interstitial tissue and relative paucity of follicles in spotted hyenas. In the proposed research I will study a group of female hyenas that were previously exposed to anti-androgens while in utero. These females are now adults and the structure and function of their ovaries will be compared to that of untreated controls. The steroidogenic responsiveness of the ovaries to a gonadotropin challenge test will be assessed in vivo, as well as in vitro (after unilateral oophorectomy). Following oophorectomy, follicle number and steroidogenic enzyme activity will be measured, and steroid receptor levels will be quantified by immunocytochemistry. This research will improve our understanding of how prenatal exposure to androgens affects ovarian structure and function.