Inter- and intra-cellular mechanisms of prostaglandin F2a action during corpus luteum regression in cattle

Abstract

The bovine corpus luteum (CL) grows very fast and regresses within a few days at luteolysis. Mechanisms controlling development and secretory function of the bovine CL may involve many factors that are produced both within and outside the CL. In the cow, luteolysis is initiated by uterine prostaglandin (PG)F2α released at the late luteal stage. It can also be induced by injection of exogenous PGF2α given at the mid luteal stage. Luteolysis consists of a phase of rapid decrease in progesterone (P4) production by the CL, followed by a phase of structural regression. Although uterine PGF2α is known to be the main luteolytic factor, its direct action on the CL is mediated by the products of accessory luteal cells: immune cells, endothelial cells, pericytes and fibroblasts. There are studies showing that beside endothelin-1, cytokines (tumor necrosis factor-α, interferons) and nitric oxide play critical roles in functional and structural luteolysis in cattle by stimulating leukotrienes and PGF2α, decreasing P4 secretion and apoptosis induction. Because of luteal blood flow and P4 concentrations decrease in parallel during both spontaneous and PGF2α-induced luteolysis, a decrease in luteal blood flow resulting in hypoxia has been proposed as one of the main luteolytic mechanisms in the cow. Hypoxia inhibits P4 synthesis in luteal cells by inhibiting the steroidogenic enzymes and promotes apoptosis of luteal cells by increasing pro-apoptotic proteins. Although reduction of luteal blood flow and hypoxia contribute to the late events of luteolysis, little is known about the physiological relevance and the cause of the transient increase in luteal blood flow and reactive oxygen species during the initial step of luteolysis.