Effects of IL‐18 on the proliferation and steroidogenesis of bovine theca cells: Possible roles in the pathogenesis of polycystic ovary syndrome

Interleukin 18 (IL‐18) is a pleiotropic pro‐inflammatory cytokine and is associated with arrested follicle development and anovulation which are the typical pathological changes of PCOS. Theca cells (TCs) have a key role in follicular growth and atresia. But whether IL‐18 can directly affect ovarian TCs function is unknown. Therefore, the objective of this study was to determine the effect of IL‐18 on proliferation and steroidogenesis of bovine TCs and to explore the biological effect of IL‐18 on folliculogenesis. This work revealed that at 300‐1000 pg/mL, IL‐18 led to a time‐ and dose‐dependently increase in cell proliferation (P < .05). IL‐18 increased 17‐hydroxyprogesterone (17OHP4) and androstenedione (A2) secretion with up‐regulation of key steroidogenesis‐related genes CYP11A1 and CYP17A1 (P < .05). Furthermore, our data demonstrated that the IL‐18R protein is predominantly expressed in small‐follicle (3‐6 mm) TCs than large follicles (8‐22 mm) by immunohistochemistry. We also found that the stimulation effects of IL‐18 on TCs can be reversed with the addition of IL‐18BP as early as at 4 hours of culture and reached the peak at 16 hours. We conclude that IL‐18 appears to target TCs in bovine, and suggest an important role for this cytokine in ovarian function. Present findings further validate potential effects of IL‐18 in the conditions associated with follicular dysplasia and excessive growth of ovarian TCs (such as PCOS). But additional research is needed to further understand the mechanism of action of IL‐18 in theca cells as well as its precise role in folliculogenesis.