Disrupting effects of lithium chloride in the rat ovary: Involves impaired formation and function of corpus luteum

Lithium is an effective drug for the treatment of bipolar disorder. Evidence suggests that lithium induces side effects on the reproductive system. We have investigated the effect of lithium chloride (LiCl) on the progesterone synthesis, the main steroid produced by corpus luteum (CL), and steroidogenic acute regulatory protein (StAR) expression, the primary mechanism of the control of CL steroidogenesis. Immature female Wistar rats (25-day-old) were injected with lithium chloride (2.0 mg/kg/day) or sterile distilled water for 15 days. All rats were induced with injection of pregnant mare’s serum gonadotrophin (PMSG) on the 13th day of experiment and followed by human chorionic gonadotropin (hCG) 48 h later. The last injection of LiCl was at 12 h post-hCG injection. Blood and ovaries were collected at 4 h interval from 12 to 24 h post-hCG injection. Serum levels of progesterone were measured by ELISA and CL formation was determined by histological analysis. Then, StAR protein and gene expression were examined using immunohistochemistry and polymerase chain reaction. Results showed the severe changes in CL formation, progesterone secretion and StAR expression in LiCl-treated rats during luteinization. It is concluded that the CL formation and the critical step of progesterone synthesis were affected by LiCl in gonadotropin-induced rat ovary.