OOCYTE COMPETENCY IN PRENATALLY ANDROGENIZED ANIMALS

描述（改编自申请人的摘要）：该提案基于的假设是，多囊卵巢综合征（PCOS）女性伴LH高分泌和高胰岛素血症的生育能力下降，部分原因是由于卵母细胞在发育和/或成熟过程中减数分裂和发育能力受损，而这些损伤与卵泡液雄激素和抑制素浓度异常有关。产前雄激素化的雌性恒河猴将作为多囊卵巢综合征的模型，因为它们表现出LH高分泌、高雄激素症、高胰岛素血症和无排卵。该提案的具体目的是确定从排卵和无排卵的成年雌性恒河猴中收集的卵母细胞是否减数分裂和发育能力受损，卵母细胞损伤是否与卵泡发生过程中异常的卵泡液或循环激素浓度有关，以及卵母细胞的体外成熟（IVM）是否可以改善其减数分裂和发育能力。卵母细胞体外受精和胚胎培养技术将评估体内LH高分泌和高胰岛素血症对卵母细胞体外减数分裂和发育能力的影响。该提案还将确定抑制素作为卵泡成熟度和卵母细胞能力的标记物的作用，以及胰岛素作为卵巢刺激期间卵泡补充的标记物的作用。实验数据将用于未来的研究，以探讨颗粒细胞来源的多肽生长/分化因子如何参与卵巢功能的调节。

DESCRIPTION (adapted from the applicant's abstract): The hypothesis upon which this proposal rests is that the reduced fertility in PCOS women with LH hypersecretion and hyperinsulinemia is caused, in part, by impaired meiotic and developmental competence of oocytes incurred during oocyte development and/or maturation, and that these impairments are associated with abnormal follicular fluid concentrations of androgens and inhibins. Prenatally androgenized female rhesus monkeys will serve as a model for PCOS because they demonstrate LH hypersecretion, hyperandrogenism, hyperinsulinemia and anovulation. The Specific Aims of the proposal are to determine whether meiotic and developmental competence are impaired in oocytes collected from ovulatory and anovulatory prenatally androgenized versus control ovulatory adult female rhesus monkeys, whether oocyte impairment is related to aberrant follicular fluid or circulating hormone concentrations during folliculogenesis, and whether in vitro maturation (IVM) of oocytes can improve their meiotic and developmental capacity. In vitro fertilization, (IVM) of oocytes and embryo culture techniques will assess the impact of LH hypersecretion and hyperinsulinemia in vivo on the meiotic and developmental competence of oocytes in vitro. This proposal also will identify the role of inhibins as markers of follicle maturity and oocyte competency and insulin as a marker of follicular recruitment during ovarian stimulation. The experimental data will be used for future studies that will investigate how polypeptide growth/differentiation factors of granulosa cell origin participate in the regulation of ovarian function.