期刊
CELL DEATH & DISEASE
卷 10, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41419-018-1208-3
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资金
- National Key Research & Developmental Program of China [2017YFC1001100, 2018YFC1003700, 2018YFC1003801]
- National Basic Research Program of China [2013CB945501, 2014CB943202, 2014CB138503]
- National Natural Science Foundation of China [31872792, 31371448, 31571540]
- Beijing Natural Science Foundation [5182015, 7182090]
- Chinese Universities Scientific Fund [2015QC018]
- Project for Young Scientists of State Key Laboratory of Agrobiotechnology [2015SKLAB4-1]
- State Key Laboratory of Agrobiotechnology [2016SKLAB-1]
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, beta-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.
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