University of Nebraska-Lincoln, School of Veterinary Medicine and Biomedical Sciences, P.O. Box 830905, Lincoln, NE, 68583-0905, USA.
University of Nebraska-Lincoln, Department of Animal Science, 3940 Fair Street, Lincoln, NE, 68583-0908, USA.
Mol Cell Endocrinol. 2021 Jul 1;531:111288. doi: 10.1016/j.mce.2021.111288. Epub 2021 Apr 24.
A naturally occurring bovine model with excess follicular fluid androstenedione (High A4), reduced fertility, and polycystic ovary syndrome (PCOS)-like characteristics has been identified. We hypothesized High A4 granulosa cells (GCs) would exhibit altered cell proliferation and/or steroidogenesis. Microarrays of Control and High A4 GCs combined with Ingenuity Pathway Analysis indicated that High A4 GCs had cell cycle inhibition and increased expression of microRNAs that inhibit cell cycle genes. Granulosa cell culture confirmed that A4 treatment decreased GC proliferation, increased anti-Müllerian hormone, and increased mRNA for CTNNBIP1. Increased CTNNBIP1 prevents CTNNB1 from interacting with members of the WNT signaling pathway thereby inhibiting the cell cycle. Expression of CYP17A1 was upregulated in High A4 GCs presumably due to reduced FOS mRNA expression compared to Control granulosa cells. Furthermore, comparisons of High A4 GC with thecal and luteal cell transcriptomes indicated an altered cellular identity and function contributing to a PCOS-like phenotype.
已经鉴定出一种具有过量卵泡液雄烯二酮（高 A4）、生育力降低和多囊卵巢综合征（PCOS）样特征的天然存在的牛模型。我们假设高 A4 颗粒细胞（GC）会表现出改变的细胞增殖和/或类固醇生成。对照和高 A4 GC 的微阵列与 Ingenuity 通路分析表明，高 A4 GC 具有细胞周期抑制作用，并且抑制细胞周期基因的 microRNA 表达增加。颗粒细胞培养证实 A4 处理可降低 GC 增殖、增加抗缪勒管激素并增加 CTNNBIP1 的 mRNA。增加的 CTNNBIP1 阻止 CTNNB1 与 WNT 信号通路的成员相互作用，从而抑制细胞周期。高 A4 GC 中 CYP17A1 的表达上调，可能是由于与对照颗粒细胞相比，FOS mRNA 表达降低所致。此外，高 A4 GC 与鞘膜和黄体细胞转录组的比较表明，细胞身份和功能的改变导致 PCOS 样表型。
