| Autor: |
Sai-Li Liu, Hai-Yang Zuo, Bing-Wang Zhao, Jia-Ni Guo, Wen-Bo Liu, Wen-Long Lei, Yuan-Yuan Li, Ying-Chun Ouyang, Yi Hou, Zhi-Ming Han, Wei-Zhou Wang, Qing-Yuan Sun, Zhen-Bo Wang |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 26, Iss 10, Pp 107828- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2023.107828 |
| Popis: |
Summary: The zona pellucida (ZP) is an extracellular glycoprotein matrix surrounding mammalian oocytes. Recently, numerous mutations in genes encoding ZP proteins have been shown to be possibly related to oocyte abnormality and female infertility; few reports have confirmed the functions of these mutations in living animal models. Here, we identified a novel heterozygous missense mutation (NM_001376231.1:c.1616C>T, p.Thr539Met) in ZP2 from a primary infertile female. We showed that the mutation reduced ZP2 expression and impeded ZP2 secretion in cell lines. Furthermore, we constructed the mouse model with the mutation (Zp2T541M) using CRISPR-Cas9. Zp2WT/T541M female mice had normal fertility though generated oocytes with the thin ZP, whereas Zp2T541M female mice were completely infertile due to degeneration of oocytes without ZP. Additionally, ZP deletion impaired folliculogenesis and caused female infertility in Zp2T541M mice. Our study not only expands the spectrum of ZP2 mutation sites but also, more importantly, increases the understanding of pathogenic mechanisms of ZP2 mutations. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
