Smith Peter, Steckler Teresa L, Veiga-Lopez Almudena, Padmanabhan Vasantha
AgResearch Wallaceville, Upper Hutt, New Zealand.
Biol Reprod. 2009 Apr;80(4):726-36. doi: 10.1095/biolreprod.108.072801. Epub 2008 Dec 17.
Prenatal testosterone excess programs an array of adult reproductive disorders including luteinizing hormone excess, functional hyperandrogenism, neuroendocrine defects, polycystic ovarian morphology, and corpus luteum dysfunction, culminating in early reproductive failure. Polycystic ovarian morphology originates from enhanced follicular recruitment and follicular persistence. We tested to determine whether prenatal testosterone treatment, by its androgenic actions, enhances follicular recruitment, causes early depletion of follicular reserve, and disrupts the ovarian architecture. Pregnant sheep were given twice-weekly injections of testosterone or dihydrotestosterone (DHT), a nonaromatizable androgen, from Days 30 to 90 of gestation. Ovaries were obtained from Day-90 and Day-140 fetuses, and from 10-mo-old females during a synchronized follicular phase (n = 5-9 per treatment). Stereological techniques were used to quantify changes in ovarian follicle/germ cell populations. Results revealed no differences in numbers of oocytes and follicles between the three groups on Fetal Day 90. Greater numbers of early growing follicles were found in prenatal testosterone- and DHT-treated fetuses on Day 140. Increased numbers of growing follicles and reduced numbers of primordial follicles were found in 10-mo-old, prenatal testosterone-treated females, but not in those treated with DHT. Antral follicles of prenatal testosterone-treated females, but not those treated with DHT, manifested several abnormalities, which included the appearance of hemorrhagic and luteinized follicles and abnormal early antrum formation. Both treatment groups showed morphological differences in the rete ovarii. These findings suggest that increased follicular recruitment and morphologic changes in the rete ovarii of prenatal testosterone-treated females are facilitated by androgenic programming, but that postpubertal follicular growth, antral follicular disruptions, and follicular depletion largely occur through estrogenic programming.
产前雄激素过量会引发一系列成年期生殖障碍，包括促黄体生成素过量、功能性高雄激素血症、神经内分泌缺陷、多囊卵巢形态以及黄体功能障碍，最终导致早期生殖功能衰竭。多囊卵巢形态源于卵泡募集增强和卵泡持续存在。我们进行了测试，以确定产前睾酮治疗通过其雄激素作用是否会增强卵泡募集、导致卵泡储备过早耗尽以及破坏卵巢结构。在妊娠第30天至90天，给怀孕的绵羊每周注射两次睾酮或二氢睾酮（DHT，一种不可芳香化的雄激素）。从妊娠90天和140天的胎儿以及处于同步卵泡期的10月龄雌性绵羊获取卵巢（每组n = 5 - 9）。采用体视学技术量化卵巢卵泡/生殖细胞群体的变化。结果显示，在胎儿90天时，三组之间的卵母细胞和卵泡数量没有差异。在140天时，产前接受睾酮和DHT治疗的胎儿中发现了更多的早期生长卵泡。在10月龄、产前接受睾酮治疗的雌性绵羊中发现生长卵泡数量增加，原始卵泡数量减少，但接受DHT治疗的雌性绵羊未出现这种情况。产前接受睾酮治疗的雌性绵羊的窦卵泡出现了一些异常，而接受DHT治疗的则没有，这些异常包括出血性和黄体化卵泡的出现以及早期窦腔形成异常。两个治疗组的卵巢网都出现了形态学差异。这些发现表明，产前接受睾酮治疗的雌性绵羊卵泡募集增加和卵巢网形态变化是由雄激素编程促成的，但青春期后卵泡生长、窦卵泡破坏和卵泡耗竭很大程度上是通过雌激素编程发生的。
