Effects of Levofloxacin on Expression of Apoptosis Genes of Ovarian Follicles in NMRI Mouse in Vitro and in Vivo

Abstract

Background and Objectives: Levofloxacin is a fluoroquinolone. Long-term use of antibiotics, including fluoroquinolone antibiotics, causes dystrophic changes in the ovaries. In this study, the effects of levofloxacin on the development of ovarian follicles and their apoptosis in the in vitro and in vivo conditions of NMRI Mouse were investigated. Methods: In the vitro study, isolated ovaries of animals were treated with levofloxacin at concentrations of 1, 2, 5, 10 µg/ml for 6 days and in the vivo study were treated with levofloxacin at concentrations of 100, 200, 400 and 800 mg/kg. After 24 days, animals were sacrificed in the in vivo groups and ovary samples were obtained. Hematoxylin and eosin (H&E) stains for histological studies also Real Time PCR techniques for study of expression rate of Bax and Bcl-2 genes were performed in both groups. Results: The results of the in vitro study showed that the dose of 2 μg/ml induced apoptosis in the monolayer primary follicles. Doses of 5 and 10 μg/ml increased the induction of apoptosis in the multilayer primary follicle. The number of secondary follicles at the 5 μg/ml dose had the most decrease. While at the dose of 10 μg/ml, the number of mature follicles had the most increase. As the antibiotic concentration increases, the expression of the Bax gene decreases and Bcl-2 gene increases significantly. The results of the in vitro study showed that the number of primary and secondary follicles decreased dose-dependently. The number of atretic follicles increased significantly with increasing dose. The expression of the Bax and Bcl-2 genes increased with increasing levofloxacin antibiotic concentration. Conclusion: This study demonstrates that levofloxacin induces apoptosis in ovarian follicles