The effect of L-Carnitine against cyclophosphamid on expression and epigenetic changes of gene Lhx8, involved in mice Premature Ovarian Failure (POF)

Abstract

Introduction: Cancer treatments with chemotherapy ugs and infertility are related topics that have received significant attention from researchers in numerous fields. Cyclophosphamide (CP) as an anti-cancer ug is frequently used to treat various types of cancer and treatment with this ug can cause reproductive toxicity. A decreased number of ovarian follicles, impaired normal ovarian function, and subsequent premature ovarian failure (POF) are presented as side effects of Cyclophosphamide. The mechanisms involved in premature ovarian failure remain unclear and a better understanding of the biology of this problem may lead to finding a treatment for preserving the follicles against the adverse effects of chemotherapy.so, we investigated the effect of L-carnitine as a widely used antioxidant in possibly protecting the ovaries. Methods: Six to week-old NMRI female mice were divided into three groups; Control, Cyclophosphamide (CP), and Cyclophosphamide / L-Carnitine (CP + L-CAR) group. After a 21-day period of ug injection, 24 hrs after the last injection ovaries were used to evaluate the expression of Sohlh1 and Lhx8 by Real-time PCR. Furthermore, alteration of Lhx8 promoter methylation was examined by Methylation-sensitive high resolution melting analysis (MS-HRM). Results: Data showed the negative effect of cyclophosphamide by altering the expression of regulators genes of oogenesis including Sohlh1 and Lhx8. Also, an examination of the epigenetic status of the Lhx8 gene shows a change in promoter methylation of this gene following cyclophosphamide injection. Although L-carnitine is an effective antioxidant, in the present study, the use of L-carnitine failed to protect the ovaries from changes caused by cyclophosphamide injection. Conclusion: These results identify that using cyclophosphamide can alter the expression of folliculogenesis genes through its effects on epigenetic changes and may cause premature ovarian failure. Our results show that L-carnitine consumption does not protect the ovaries against cyclophosphamide.