College of Veterinary Medicine, Yangzhou University, Yangzhou, Jiangsu, 225009, People's Republic of China.
State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, 100193, Beijing, People's Republic of China.
BMC Biol. 2024 Aug 26;22(1):176. doi: 10.1186/s12915-024-01957-3.
Casein kinase 1α (CK1α), expressed in both ovarian germ and somatic cells, is involved in the initial meiosis and primordial follicle formation of mouse oocytes. Using in vitro and in vivo experiments in this study, we explored the function and mechanism of CK1α in estrogen synthesis in mice ovarian granulosa cells.
A CK1α knockout (cKO) mouse model, targeted specifically to ovarian granulosa cells (GCs), was employed to establish the influence of CK1α on in vivo estrogen synthesis. The influence of CK1α deficiency on GCs was determined in vivo and in vitro by immunofluorescence analysis and Western blot assay. Transcriptome profiling, differentially expressed genes and gene functional enrichment analyses, and computation protein-protein docking, were further employed to assess the CK1α pathway. Furthermore, wild-type female mice were treated with the CK1α antagonist D4476 to elucidate the CK1α's role in estrogen regulation.
Ovarian GCs CK1α deficiency impaired fertility and superovulation of female mice; also, the average litter size and the estradiol (E) level in the serum of cKO female mice were decreased by 57.3% and 87.4% vs. control mice, respectively. This deficiency disrupted the estrous cycle and enhanced the apoptosis in the GCs. We observed that CK1α mediated the secretion of estradiol in mouse ovarian GCs via the cytochrome P450 subfamily 19 member 1 (CYP19A1).
These findings improve the existing understanding of the regulation mechanism of female reproduction and estrogen synthesis.
Not applicable.
酪蛋白激酶 1α（CK1α）在卵巢生殖细胞和体细胞中均有表达，参与小鼠卵母细胞的初次减数分裂和原始卵泡形成。本研究通过体外和体内实验，探讨 CK1α 对小鼠卵巢颗粒细胞（GCs）中雌激素合成的作用及机制。
采用靶向特异性敲除卵巢 GC 中 CK1α 的 CK1α 敲除（cKO）小鼠模型，建立 CK1α 对体内雌激素合成影响的模型。通过免疫荧光分析和 Western blot 检测，评估 CK1α 缺失对体内和体外 GC 的影响。进一步进行转录组谱分析、差异表达基因和基因功能富集分析、计算蛋白-蛋白对接，评估 CK1α 通路。此外，用 CK1α 拮抗剂 D4476 处理野生型雌性小鼠，以阐明 CK1α 在雌激素调节中的作用。
卵巢 GC 中 CK1α 的缺失损害了雌性小鼠的生育能力和超排卵；与对照组小鼠相比，cKO 雌性小鼠的平均窝仔数和血清雌二醇（E）水平分别降低了 57.3%和 87.4%。这种缺失破坏了动情周期，增加了 GC 的凋亡。我们观察到 CK1α 通过细胞色素 P450 家族 19 亚家族成员 1（CYP19A1）介导了小鼠卵巢 GC 中雌二醇的分泌。
这些发现提高了我们对女性生殖和雌激素合成调节机制的现有认识。
不适用。
