Melatonin provides protection against cisplatin-induced ovarian damage and loss of fertility in mice

Abstract

Research questionCan melatonin provide non-invasive ovarian protection against damage caused by cis-diamminedichloroplatinum (cisplatin) and preserve fertility in female cancer patients? And if so, what is the possible mechanism? DesignAthymic BALB/c nude tumour-bearing female mice were used to demonstrate whether melatonin affects the antineoplastic effect when co-administrated with cisplatin. Sexually mature and newborn C57BL/6 female mice were used to evaluate the potential effects of melatonin on the ovarian follicle pool, pregnancy rate and litter number in cisplatin-treated mice. The ovaries underwent immunohistochemical, TdT (terminal deoxynucleotidyl transferase)-mediated dUTP nick-end labelling (TUNEL) and gene array analysis to explore the underlying mechanism. In addition, granulosa cells were isolated to investigate the potential protective mechanism of melatonin. ResultsMelatonin not only enhanced the anti-cancer effect of cisplatin in tumour-bearing nude mice, but also reduced ovarian toxicity and preserved long-term fertility in cisplatin-treated C57BL/6 female mice. When co-administrated, melatonin was able to reduce the DNA damage and toxic effects on lipid peroxidation in the ovaries caused by cisplatin. Specifically, melatonin was able to largely restore lipid peroxidation in granulosa cells and thus prevent ovarian follicles from being depleted. ConclusionsMelatonin has the potential to be used as a chemotherapeutic adjuvant to simultaneously improve the outcome of anti-cancer treatment and preserve ovarian function during cisplatin chemotherapy. Notably, its properties of DNA protection and antioxidant effects on follicles may benefit female cancer survivors and prevent premature ovarian failure as well as fertility loss caused by chemotherapy.