Melatonin Ameliorates Cyclophosphamide-Induced Spermatogenesis Disorder by Reducing Pyroptosis

As a chemotherapeutic drug, cyclophosphamide (CP) has negative impact on male fertility due to its reproductive toxicity. Melatonin (Mel) promotes the system and increases testosterone synthesis. This study is aimed at exploring molecular mechanism of Mel as protector against CP-induced cytotoxicity. A CP toxicity model was established in adult ICR mice by intraperitoneal injection 100 mg/kg every other day for week. Protective effects testis from damage were evaluated using four groups that received injections normal saline, CP, 10 Mel, or same dosage respectively. Testis morphology observed hematoxylin eosin (HE) staining. Sperm quality parameters evaluated, sperm function studied vitro fertilization (IVF). Proliferation, meiosis, pyroptosis markers examined western blot. Results showed treatment induced time-dependent manner with most severe two weeks post treatment. CP-treated reduced testicular weight impaired spermatogenesis downregulating PCNA SYCP3, serum levels, decreased counts motility, increased seminiferous tubule vacuolization, oxidative spermatogenic cells. All these effects, apart weight, could be ameliorated administration. The IVF experiment revealed rates blastocyst development, which also enhanced Mel. Mel-treated expression proliferation-associated protein meiosis-associated proteins REC8, STRA8, all CP. Furthermore, inhibited cells reducing GSDMD IL18 expression. In conclusion, this indicated might protect DNA germ through alleviation pyroptosis.