Reproductive diseases in dairy cows as cystic ovarian disease (COD) represent a major problem that impacts on dairy production. COD is characterized by anovulation, persistence of the dominant follicle, and interruption of normal estrous cycles. Anovulation is attributable to a failure in the LH surge, due to endocrine imbalances and alterations in local factors, such as the insulin signaling pathway. Thus, the aim of this study was to examine the expression of critical nodes of the insulin pathway, including insulin receptor (IR), IR substrate (IRS), phosphatidylinositol-3-kinase (PI3K), and protein kinase B (also known as Akt or pan-Akt), in ovarian follicular structures of cows during the development of follicular persistence induced by long-term progesterone administration. Immunoexpression of IR, p-IR, IRS1, p-IRS1, PI3K, pan-Akt and p-pan-Akt was evaluated in situ by immunohistochemistry and the concentration of insulin in serum and follicular fluid was determined by radioimmunoassay. p-IR, p-IRS1, PI3K and p-pan-Akt expression was decreased in follicles at different times of persistence in relation to the control dominant follicles, in both granulosa and theca cells, whereas IR and IRS1 immunoexpression was decreased in persistent follicles at 5 and 15 days of persistence in granulosa cells. Serum and follicular fluid insulin concentration was higher in cows with persistent follicles than in control cows. These results show that decreased expression and/or activation of the receptors and other intermediates of the insulin signaling pathway in persistent follicles indicates that reduced response/resistance to insulin rather than the concentration of insulin per se may be one of the important molecular mechanisms in the development of persistent follicles in dairy cows.

中文翻译：

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实验诱导卵泡持久性的牛卵巢胰岛素信号通路的改变

奶牛的生殖疾病如囊性卵巢疾病 (COD) 是影响奶牛生产的主要问题。COD 的特点是无排卵、优势卵泡持续存在和正常发情周期中断。由于内分泌失衡和局部因素（例如胰岛素信号通路）的改变，导致 LH 激增失败，导致无排卵。因此，本研究的目的是检查胰岛素通路关键节点的表达，包括胰岛素受体 (IR)、IR 底物 (IRS)、磷脂酰肌醇 3-激酶 (PI3K) 和蛋白激酶 B（也称为Akt 或 pan-Akt)，在长期服用黄体酮诱导的卵泡持续性发育过程中奶牛的卵巢卵泡结构中。IR、p-IR、IRS1、p-IRS1、PI3K、pan-Akt 和 p-pan-Akt 通过免疫组织化学原位评估，血清和卵泡液中的胰岛素浓度通过放射免疫测定法测定。p-IR、p-IRS1、PI3K 和 p-pan-Akt 表达在不同持续时间的卵泡中相对于对照优势卵泡（颗粒和膜细胞）降低，而 IR 和 IRS1 免疫表达在持续卵泡中降低在颗粒细胞中持续 5 天和 15 天。具有持久卵泡的奶牛的血清和卵泡液胰岛素浓度高于对照奶牛。