Although hormonal regulation of ovarian follicle development has been extensively investigated, most studies concentrate on the development of early antral follicles to the preovulatory stage, leading to the successful use of exogenous FSH for infertility treatment. Accumulating data indicate that preantral follicles are under stringent regulation by FSH and local intraovarian factors, thus providing the possibility to develop new therapeutic approaches. Granulosa cell-derived C-type natriuretic factor not only suppresses the final maturation of oocytes to undergo germinal vesicle breakdown before ovulation but also promotes preantral and antral follicle growth. In addition, several oocyte- and granulosa cell-derived factors stimulate preantral follicle growth by acting through wingless, receptor tyrosine kinase, receptor serine kinase, and other signaling pathways. In contrast, the ovarian Hippo signaling pathway constrains follicle growth and disruption of Hippo signaling promotes the secretion of downstream CCN growth factors capable of promoting follicle growth. Although the exact hormonal factors involved in primordial follicle activation has yet to be elucidated, the protein kinase B (AKT) and mammalian target of rapamycin signaling pathways are important for the activation of dormant primordial follicles. Hippo signaling disruption after ovarian fragmentation, combined with treating ovarian fragments with phosphatase and tensin homolog (PTEN) inhibitors and phosphoinositide-3-kinase stimulators to augment AKT signaling, promote the growth of preantral follicles in patients with primary ovarian insufficiency, leading to a new infertility intervention for such patients. Elucidation of intraovarian mechanisms underlying early folliculogenesis may allow the development of novel therapeutic strategies for patients diagnosed with primary ovarian insufficiency, polycystic ovary syndrome, and poor ovarian response to FSH stimulation, as well as for infertile women of advanced reproductive age.

中文翻译：

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早期卵泡发生的卵巢内控制。

尽管已对卵巢卵泡发育的激素调节进行了广泛研究，但大多数研究集中在早期窦卵泡发育至排卵前阶段，从而成功使用外源性 FSH 治疗不孕症。越来越多的数据表明，窦前卵泡受到 FSH 和局部卵巢内因素的严格调控，从而为开发新的治疗方法提供了可能。颗粒细胞衍生的 C 型利钠因子不仅抑制卵母细胞在排卵前进行生泡破裂的最终成熟，而且还促进窦前和窦卵泡的生长。此外，几种卵母细胞和颗粒细胞衍生因子通过无翅受体酪氨酸激酶、受体丝氨酸激酶、和其他信号通路。相反，卵巢 Hippo 信号通路限制卵泡生长，Hippo 信号通路的破坏促进下游 CCN 生长因子的分泌，从而促进卵泡生长。尽管参与原始卵泡激活的确切激素因素尚未阐明，但蛋白激酶 B (AKT) 和雷帕霉素信号通路的哺乳动物靶点对于激活休眠的原始卵泡很重要。卵巢破碎后 Hippo 信号传导中断，结合用磷酸酶和张力蛋白同系物 (PTEN) 抑制剂和磷酸肌醇-3-激酶刺激剂处理卵巢碎片以增强 AKT 信号，促进原发性卵巢功能不全患者的窦前卵泡生长，导致新的对此类患者进行不孕干预。