Jia Huang1, Wanying Shan1, Na Li1, Bo Zhou1, Ensong Guo1, Meng Xia1, Hao Lu1, Yifan Wu1, Jing Chen1, Beibei Wang1, Ling Xi1, Ding Ma1, Gang Chen1, Kezhen Li2, Chaoyang Sun3. 1. Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China. 2. Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China. Electronic address: tjkeke@126.com. 3. Department of Gynecology and Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan Hubei, China. Electronic address: suncydoctor@gmail.com.
Abstract
RESEARCH QUESTION: Can 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? DESIGN: Athymic 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. RESULTS: Melatonin 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. CONCLUSIONS: Melatonin 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.
RESEARCH QUESTION: Can melatonin provide non-invasive ovarian protection against damage caused by cis-diamminedichloroplatinum (cisplatin) and preserve fertility in female cancerpatients? And if so, what is the possible mechanism? DESIGN: Athymic 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. RESULTS:Melatonin 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. CONCLUSIONS:Melatonin 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.
Authors: Javier Egea; Francisco López-Muñoz; Oscar Fernández-Capetillo; Russel J Reiter; Alejandro Romero Journal: Front Pharmacol Date: 2022-03-23 Impact factor: 5.810