Pepe Gerald J, Billiar Reinhart B, Albrecht Eugene D
Department of Physiological Sciences, Eastern Virginia Medical School, Norfolk, VA 23501-1980, USA.
Mol Cell Endocrinol. 2006 Mar 9;247(1-2):41-6. doi: 10.1016/j.mce.2005.11.045. Epub 2006 Jan 18.
Although it is well established that formation of the pool of follicles available for ovarian function and fertility in adulthood in human and non human primates occurs in utero, our understanding of the regulation of fetal ovarian development is incomplete. Our laboratories have been instrumental in establishing the baboon as a model for the study of human reproductive endocrinology and showed that estrogen plays a central integrative role in regulating fetal-placental development. Therefore, we adapted our baboon model to study the role of estrogen on fetal ovarian development. Estrogen receptors alpha and beta were expressed in pregranulosa cells and interfollicular nests of the baboon fetal ovary. In baboons in which estrogen levels had been suppressed by administration of an aromatase inhibitor throughout the second half of gestation, fetal ovarian follicle numbers were reduced by 50%, whereas the number of interfollicular nests comprised of oocytes and pregranulosa cells was increased. The decrease in follicles in estrogen-deprived animals was associated with a marked upregulation of expression of alpha-inhibin, but not activins or activin receptors and signaling molecules. Moreover, the majority of the follicles formed in ovaries of estrogen-depleted fetuses appeared unhealthy and contained oocytes with a marked reduction/depletion in microvilli, structures essential for uptake of substrates from surrounding granulosa cells. We propose that estrogen regulates fetal ovarian folliculogenesis and formation of healthy oocytes by controlling the intraovarian activin:inhibin ratio and the development of oocyte microvilli. These findings demonstrate a need for translational research studies of the impact of impairment of estrogen action/availability on reproductive function in adulthood.
尽管已有充分证据表明，人类和非人灵长类动物成年后可用于卵巢功能和生育的卵泡池是在子宫内形成的，但我们对胎儿卵巢发育调节的理解仍不完整。我们的实验室在将狒狒确立为人类生殖内分泌学研究模型方面发挥了重要作用，并表明雌激素在调节胎儿 - 胎盘发育中起着核心整合作用。因此，我们调整了狒狒模型来研究雌激素对胎儿卵巢发育的作用。雌激素受体α和β在狒狒胎儿卵巢的颗粒前体细胞和卵泡间巢中表达。在整个妊娠后半期通过给予芳香化酶抑制剂抑制雌激素水平的狒狒中，胎儿卵巢卵泡数量减少了50%，而由卵母细胞和颗粒前体细胞组成的卵泡间巢数量增加。雌激素缺乏动物卵泡数量的减少与α - 抑制素表达的显著上调有关，但激活素、激活素受体和信号分子的表达没有上调。此外，雌激素缺乏胎儿卵巢中形成的大多数卵泡看起来不健康，其卵母细胞的微绒毛明显减少/缺失，而微绒毛是从周围颗粒细胞摄取底物所必需的结构。我们提出，雌激素通过控制卵巢内激活素：抑制素的比例和卵母细胞微绒毛的发育来调节胎儿卵巢卵泡发生和健康卵母细胞的形成。这些发现表明需要开展转化研究，以探讨雌激素作用/可利用性受损对成年期生殖功能的影响。
