Abstract
Most of the clinically infertile patients show spermatogenesis dysfunction. Cyclophosphamide, as an anticancer drug, can induce spermatogenesis dysfunction. Sesamin is the main bioactive component of natural lignans in sesame. It is abundant in sesame oil and has strong biological activities such as antioxidant, antibacterial, and hypoglycemic properties. By establishing the model of spermatogenic dysfunction induced by cyclophosphamide in male mice and then feeding sesamin (50, 100, and 200 mg/kg) for 2 weeks, we proved that sesamin can improve the reproductive organ damage induced by cyclophosphamide and increase the number and activity of sperms. Sesamin can resist cyclophosphamide-induced sperm nuclear maturity and DNA damage by increasing the expression levels of histones H2A and H2B in the testis. In addition, sesamin can improve the ubiquitination of histones regulated by RNF8 to protect the testis. In conclusion, these results suggest that sesamin can improve spermatogenic dysfunction induced by cyclophosphamide, which may be mediated by ubiquitination of histones.
Highlights
Infertility is a reproductive dysfunction recognized by the clinical failure of pregnancy after 1 year or more of regular unprotected sexual intercourse (Zegers-Hochschild et al, 2009a)
In the CTX group, the number and morphology of spermatogenic cells at all levels in the testis did not change during the early stages of spermatogenesis, I–VI, while the number of mature spermatogenic cells entering the lumen decreased during the stages VII–VIII and the number of spermatogenic cells decreased during the deformable stages IX–XII, indicating that CTX mainly affected the late stage of spermatogenesis
In order to understand the specific underlying mechanism, we examined each stage of the spermatogenic epithelial cell cycle by hematoxylin and eosin (H&E) staining, which showed that spermatogenesis was blocked during spermatogenesis and the number of concentrated spermatids in seminiferous tubules of CTX-exposed mice was greatly reduced, which was recovered by sesamin treatment
Summary
Infertility is a reproductive dysfunction recognized by the clinical failure of pregnancy after 1 year or more of regular unprotected sexual intercourse (Zegers-Hochschild et al, 2009a). For the past 40 years, more than 50% of the total number and concentration of sperms has decreased in multiple countries up to date (Zegers-Hochschild et al, 2009b). It affects about 15% of couples of reproductive age, having failed pregnancy within a 12-month period under regular sexual intercourse (Punab et al, 2016). Increasing research indicates that most of the infertile patients showed spermatogenesis dysfunction.
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