Oocyte-derived E-cadherin acts as a multiple functional factor maintaining the primordial follicle pool in mice

Autor: Qirui Guo, Guangcun Deng, Chao Wang, Hua Zhang, Zhiqing Wei, Meina He, Guoliang Xia, Hao Yan, Qian Chen, Kun Huang, Wenying Zheng, Tuo Zhang, Jinrui Xu, Yi Yang, Jia Wen
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Zdroj: Cell Death and Disease, Vol 10, Iss 3, Pp 1-14 (2019)
Cell Death & Disease
ISSN: 2041-4889
Popis: In mammals, female fecundity is determined by the size of the primordial follicle (PF) pool, which is established during the perinatal period. As a non-renewable resource, the preservation of dormant PFs is crucial for sustaining female reproduction throughout life. Although studies have revealed that several oocyte-derived functional genes and pathways, such as newborn ovary homeobox (NOBOX) and 3-phosphoinositide-dependent protein kinase-1, participate in maintaining the PF pool, our understanding of the underlying molecular mechanisms is still incomplete. Here, we demonstrate that E-cadherin (E-cad) plays a crucial role in the maintenance of PFs in mice. E-cad is specifically localized to the cytomembrane of oocytes in PFs. Knockdown of E-cad in neonatal ovaries resulted in significant PF loss owing to oocyte apoptosis. In addition, the expression pattern of NOBOX is similar to that of E-cad. Knockdown of E-cad resulted in a decreased NOBOX level, whereas overexpression of Nobox partially rescued the follicle loss induced by silencing E-cad. Furthermore, E-cad governed NOBOX expression by regulating the shuttle protein, β-catenin, which acts as a transcriptional co-activator. Notably, E-cad, which is a transmembrane protein expressed in the oocytes, was also responsible for maintaining the PF structure by facilitating cell–cell adhesive contacts with surrounding pregranulosa cells. In conclusion, E-cad in oocytes of PFs plays an indispensable role in the maintenance of the PF pool by facilitating follicular structural stability and regulating NOBOX expression. These findings shed light on the physiology of sustaining female reproduction.
Databáze: OpenAIRE