Effect of conditional YY1 knockout in vascular endothelial cells on ovarian function in mice and its mechanism
10.13200/j.cnki.cjb.004334
- VernacularTitle:血管内皮细胞YY1条件性敲除对小鼠卵巢功能的影响及其作用机制
- Author:
WANG Na
- Publication Type:Journal Article
- Keywords:
Vascular endothelial cells;
YY1;
Ovarian function;
Angiogenesis;
CreER~(T2)/LoxP system
- From:
Chinese Journal of Biologicals
2024;37(11):1307-1312
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of conditional YY1 knockout in vascular endothelial cells on ovarian function in mice and its mechanism, so as to provide a new target and strategy for the diagnosis and treatment of infertility caused by angiogenesis disorder. Methods YY1~(flox/flox)(WT) and Cdh5-CreER~(T2)mice were constructed by CreER~(T2)/LoxP system, and then mated to obtain the YY1 vascular endothelial conditional knockout mice(Cdh5-CreER~(T2); YY1~(flox/flox), referred to as YY1~(i△EC)). The genotypes were identified by PCR. By administering tamoxifen to YY1~(iΔEC)mice to induce Cre enzyme activity,temporal-specific knockout of YY1 in vascular endothelial cells was achieved. After knockout for one month, the mouse pulmonary vascular endothelial cells were isolated, and the knockout efficiency was verified by immunofluorescence and Western blot. Using WT female mice as control, the YY1~(i△EC)female mice after knockout were detected for the fertility, estrous cycle and ovary angiogenesis, and observed for the ovary and uterus. Results After knockout of YY1 for one month, the number of vascular endothelial cells in YY1~(i△EC)mice decreased, and YY1 in vascular endothelial cells was knocked out efficiently and specifically. Compared with WT female mice, the ability of female YY1~(i△EC)mice to conceive and give birth to cubs was greatly reduced; the female YY1~(iΔEC)mice exhibited disrupted estrous cycles, and had spontaneous ovulation and impaired formation of corpus luteum; the ovarian angiogenesis was significantly inhibited(F = 1. 288, P < 0. 01); the ovary and uterus were small in size, and the ovary was pale in color and lacked corpus luteum on the surface. Conclusion Conditional YY1knockout in vascular endothelial cells can cause reproductive dysfunction in mice, which may be due to the inhibition of ovarian angiogenesis by vascular endothelial cell YY1 deficiency, resulting in impaired ovulation and luteinization function.
