Mechanism of Lithium’s Effect on Follicular Development of the Rat Ova

• Main Authors: Ghamartaj Hossein, Mohammad Reza Baghaban Eslaminejad, Azita Parvaneh Tafreshi, Fahimeh Mirakhori, Bahman Zeynali, Ameneh Shirmohamadian
• Format: Article
• Language: English
• Published: Royan Institute (ACECR), Tehran 2010-01-01
• Series: Cell Journal
• Subjects: Lithium Chloride; Apoptosis; Ovarian Follicle; Immature Rat
• Online Access: http://celljournal.org/library/upload/article/af_4346625Mirakhori.pdf

Objective: It has been shown that lithium chloride (LiCl), an effective drug for the treatmentof bipolar disorder, has side effects on the female reproductive system. In this study,cellular and histological effects of lithium chloride on the development of ovarian folliclesin immature female rats were investigated.Materials and Methods: To induce ovarian follicular development, twenty-three day oldimmature female rats were injected with 10 IU of pregnant mare serum gonadotropin(PMSG), followed by four doses of LiCl (250 mg/kg/dose) each injected every 12 hours,starting from the time of the PMSG injection. The rat ovaries were removed 48 hours afterthe PMSG injection and prepared for histological, immunohistochemical, and DNA ladderingstudies. Control immature female rats received only PMSG, while sham treated ratsreceived PMSG and physiological serum (lithium vehicle).Results: Our results showed that in the ovaries of LiCl-treated rats there were neitherlarge antral follicles (800-1000 μm) nor fewer medium sized follicles (400-800 μm) but aincreased number of atretic follicles compared to those in the control rats. The inductionof atresia in the ovaries of LiCl-treated rats was further confirmed by the presence of DNAfragmentation. Looking at the cellular levels, lithium extremely significant (p<0.0001) increasedthe number of TUNEL-positive cells in the granulosa layer of the antral follicles.Conclusion: Taken together, our results suggest that lithium may decrease folliculogenesisby inducing apoptosis in the antral follicles.