Asynchronous embryonic germ cell development leads to a heterogeneity of postnatal ovarian follicle activation and may influence the timing of puberty onset in mice
Yanli Dai,
Yingnan Bo,
Peike Wang,
Xueqiang Xu,
Meenakshi Singh,
Longzhong Jia,
Shuo Zhang,
Shudong Niu,
Kaixin Cheng,
Jing Liang,
Lu Mu,
Kaiying Geng,
Guoliang Xia,
Chao Wang,
Yan Zhang,
Hua Zhang
Affiliations
Yanli Dai
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Yingnan Bo
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Peike Wang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Xueqiang Xu
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Meenakshi Singh
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg
Longzhong Jia
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Shuo Zhang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Shudong Niu
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Kaixin Cheng
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Jing Liang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Lu Mu
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Kaiying Geng
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Guoliang Xia
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Chao Wang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Yan Zhang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Hua Zhang
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Abstract Background 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. Results 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. Conclusion 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.
