Melatonin ameliorates paclitaxel‐induced mice spermatogenesis and fertility defects

Abstract

Chemotherapeutic drug of paclitaxel (PTX) has been shown to cause reproductive toxicity thus affecting male fertility, but its underlying molecular basis is unclear. Melatonin (MLT) can mitigate the reproductive damage caused by certain chemotherapy drugs. In this study, we aimed to identify impact of PTX on the main biological processes and protective effect of MLT on reproductive damage caused by PTX. Mice exposed to PTX mainly impaired spermatogenesis, such as decreased sperm counts, reduced sperm motility and increased abnormal sperm. Decreased expressions of germ cell proliferation‐associated protein PCNA and meiosis‐related protein SYCP3 induced by PTX were determined by Western blot, while MLT ameliorated this effect and increased the expressions of PCNA, SYCP3, DMC1, STRA8 and fertility‐related protein of HSPA2, resulting in significantly improved spermatogenesis and sperm quality levels. In vitro fertilization experiment showed that PTX significantly decreased blastocyst formation rates, which can be improved by MLT administration, but not two‐cell development rates. Taken together, this work demonstrated PTX can adversely affect germ cell proliferation and meiosis, which ultimately influence sperm quality and male fertility, and highlighted the protective ability of MLT on ameliorating the side effects of PTX, especially on sperm quality. The results provide information to further the study on the molecular mechanism of PTX's effects on male reproduction and the protective mechanism of MLT.

Melatonin Relieves Paclitaxel-Induced Neuropathic Pain by Regulating pNEK2-Dependent Epigenetic Pathways in DRG Neurons

“…The histone H3K27 demethylase JMJD3 (KDM6B) affects the fragmentation of spermatogonial cysts . Notably, MLT can mitigate the reproductive damage caused by certain chemotherapy drugs . MLT had a protective role against Taxol-induced testicular cytotoxicity, which may be a result of inhibition of testicular apoptosis .…”

Protective effect of melatonin on alleviating early oxidative stress induced by DOX in mice spermatogenesis and sperm quality maintaining

“…Group 4 (MLT + DOX treated, 35 mice): Mice received 10 mg/kg DOX (body weight/day) on day 1 of the experiment and 10 mg/kg of intraperitoneal MLT for several consecutive days. DOX and melatonin dosing were based on previously published articles [ 23 , 24 ]. Mice were anesthetized for the experiments at different time points (day 3, day 5, week 1, week 2, week 3, week 4 and week 5) following drug administration.…”

Endocrine disorders and fertility and pregnancy: An update

“…There are also studies linking melatonin to male fertility in animals (46). Protective effect on gonads has been demonstrated in the course of varicocele, radiotherapy and metabolic syndrome, exposure to cytostatics and heavy metals (47,(116)(117)(118)(119).…”

“…The relationship between melatonin receptors polymorphism and female fertility has been proven ( 32 , 39 – 41 ). There are also numerous reports suggesting a protective effect of melatonin administration on fertility, maintenance of pregnancy and prevention of birth defects in females exposed to cytostatics, insecticides, herbicides and alcohol ( 42 – 46 ), which is directly related to its antioxidant nature.…”