State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 100193, China.
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, SE-405 30, Gothenburg, Sweden.
BMC Biol. 2022 May 13;20(1):109. doi: 10.1186/s12915-022-01318-y.
Ovarian follicles, which are the basic units of female reproduction, are composed of oocytes and surrounding somatic (pre) granulosa cells (GCs). A recent study revealed that signaling in somatic preGCs controlled the activation (initial recruitment) of follicles in the adult ovaries, but it is also known that there are two waves of follicle with age-related heterogeneity in their developmental dynamics in mammals. Although this heterogeneity was proposed to be crucial for female reproduction, our understanding of how it arises and its significance is still elusive.
In the current study, by deleting the key secreted factor KIT ligand from preGCs and analyzing the follicle cell developmental dynamics, we revealed distinct patterns of activation and growth associated with the two waves of follicles in mouse ovary. Our results confirmed that activation of adult wave follicles is initiated by somatic preGCs and dependent on the KIT ligand. By contrast, activation of first wave follicles, which are awakened from germ cells before follicle formation, can occur in the absence of preGC-secreted KIT ligand in postnatal ovaries and appears to be oocyte-initiated. We also found that the asynchronous activity of phosphatidylinositol 3 kinases (PI3K) signaling and meiotic process in embryonic germ cells lead to the follicle heterogeneity in postnatal ovaries. In addition, we supplied evidence that the time sequence of embryonic germ cell development and its related first wave follicle growth are correlated to the time of puberty onset in females.
Taken together, our study provides evidence that asynchronous development of embryonic oocytes leads to the heterogeneity of postnatal ovarian follicle activation and development, and affects the timing of onset of puberty in females.
卵巢卵泡是女性生殖的基本单位，由卵母细胞和周围的体（前）颗粒细胞（GCs）组成。最近的一项研究表明，体前 GC 中的信号控制了成年卵巢中卵泡的激活（初始募集），但已知哺乳动物的卵泡在发育动力学上存在与年龄相关的两波异质性。尽管这种异质性被认为对女性生殖至关重要，但我们对其产生的方式及其意义仍知之甚少。
在本研究中，通过从体前 GC 中删除关键的分泌因子 KIT 配体，并分析卵泡细胞的发育动力学，我们揭示了与小鼠卵巢中两波卵泡相关的不同激活和生长模式。我们的研究结果证实，成年波卵泡的激活是由体前 GC 启动的，并且依赖于 KIT 配体。相比之下，第一波卵泡的激活可以在卵泡形成前从生殖细胞中唤醒，并且可以在出生后卵巢中缺乏前 GC 分泌的 KIT 配体的情况下发生，似乎是卵母细胞启动的。我们还发现，胚胎生殖细胞中磷脂酰肌醇 3 激酶（PI3K）信号和减数分裂过程的异步活性导致了出生后卵巢中卵泡的异质性。此外，我们提供的证据表明，胚胎生殖细胞发育的时间顺序及其相关的第一波卵泡生长与雌性青春期开始的时间相关。
综上所述，我们的研究提供了证据表明，胚胎卵母细胞的异步发育导致了出生后卵巢卵泡激活和发育的异质性，并影响了雌性青春期开始的时间。
