A Role for Orphan Nuclear Receptor Liver Receptor Homolog-1 (LRH-1, NR5A2) in Primordial Follicle Activation

The ovarian reserve of follicles comprises all oocytes for lifetime fertility and is depleted by progressive activation. The orphan nuclear receptor liver receptor homolog 1 (LRH-1; Nr5a2) is essential for ovulation, but its role in the early stages of follicular development is not known. We therefore developed a model of conditional depletion of LRH-1 from early postnatal ovaries (postnatal day 4) and performed RNAsequencing to identify LRH-1 regulated genes during the earliest stages of follicular activation. Mice with ovarian knockout of liver receptor homolog 1 (LRH-1) were generated using Amhr2-cre (LRH-1 cKO; Nr5a2 f/f, Amhr2-cre Tg/+) and compared to littermate controls with intact LRH-1 expression (Con; Nr5a2 f/f, Amhr2-cre +/+). Ovaries were collected from mice on postnatal day (PND) 4.卵泡储备包含支撑雌性终生生育能力的全部卵母细胞，并随卵泡的渐进性激活而逐渐耗竭。孤儿核受体肝受体同源物1（liver receptor homolog 1，LRH-1；Nr5a2）对排卵过程至关重要，但其在卵泡发育早期阶段的作用尚未明确。为此，我们构建了出生后早期（出生后第4天）卵巢中LRH-1条件性敲除的模型，并通过RNA测序（RNA sequencing）鉴定卵泡激活最早阶段受LRH-1调控的基因。本研究利用Amhr2-cre系统构建了卵巢特异性敲除肝受体同源物1（LRH-1）的小鼠（LRH-1 cKO；Nr5a2 f/f, Amhr2-cre Tg/+），并与LRH-1表达完整的同窝对照小鼠（Con；Nr5a2 f/f, Amhr2-cre +/+）进行对照分析。实验中，我们收集了出生后第4天（PND 4）的小鼠卵巢组织。