Alterations in the insulin signaling pathway in bovine ovaries with experimentally induced follicular persistence

Abstract

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.