Casein kinase 1α mediates estradiol secretion via CYP19A1 expression in mouse ovarian granulosa cells.

IF 4.4 1区 生物学 Q1 BIOLOGY BMC Biology Pub Date : 2024-08-26 DOI:10.1186/s12915-024-01957-3
Xuan Luo, Di Zhang, Jiaming Zheng, Hui Liu, Longjie Sun, Hongzhou Guo, Lei Wang, Sheng Cui
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Abstract

Background: 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.

Methods: 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.

Results: Ovarian GCs CK1α deficiency impaired fertility and superovulation of female mice; also, the average litter size and the estradiol (E2) 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).

Conclusions: These findings improve the existing understanding of the regulation mechanism of female reproduction and estrogen synthesis.

Trial registration: Not applicable.

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酪蛋白激酶 1α 通过 CYP19A1 在小鼠卵巢颗粒细胞中的表达介导雌二醇分泌。
背景: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始减数分裂和原始卵泡的形成。本研究通过体外和体内实验,探讨了CK1α在小鼠卵巢颗粒细胞雌激素合成中的功能和机制:方法:采用CK1α基因敲除(cKO)小鼠模型,特别针对卵巢颗粒细胞(GCs),以确定CK1α对体内雌激素合成的影响。通过免疫荧光分析和 Western 印迹检测确定了体内和体外 CK1α 缺乏对 GCs 的影响。通过转录组分析、差异表达基因和基因功能富集分析以及计算蛋白-蛋白对接,进一步评估了CK1α通路。此外,还用CK1α拮抗剂D4476处理野生型雌性小鼠,以阐明CK1α在雌激素调控中的作用:结果:卵巢GCs CK1α缺乏会影响雌性小鼠的生育能力和超排卵能力;与对照组相比,cKO雌性小鼠的平均窝产仔数和血清中的雌二醇(E2)水平分别下降了57.3%和87.4%。这种缺乏会扰乱发情周期,并加剧GCs的凋亡。我们观察到,CK1α通过细胞色素P450亚家族19成员1(CYP19A1)介导了小鼠卵巢GCs中雌二醇的分泌:这些发现加深了人们对女性生殖和雌激素合成调控机制的理解:试验注册:不适用。
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来源期刊
BMC Biology
BMC Biology 生物-生物学
CiteScore
7.80
自引率
1.90%
发文量
260
审稿时长
3 months
期刊介绍: BMC Biology is a broad scope journal covering all areas of biology. Our content includes research articles, new methods and tools. BMC Biology also publishes reviews, Q&A, and commentaries.
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