Investigation of TAp63 gene expression and follicle count using melatonin in cisplatin-induced ovarian toxicity

Hacı Öztürk Şahin, Mehmet Nuri Duran, Fatma Sılan, Ece Sılan, Duygu Sıddıkoglu, Nihal Kılınç


Background: Premature ovarian failure is among the most important side effects of chemotherapy during reproductive period. Preserving ovarian function is gradually gaining importance during oncologic treatment. The present study aims to investigate the potential of melatonin to protect from cisplatin-induced ovarian toxicity in rats.

Methods: Twenty-nine female rats were divided to three groups: Saline control group (group 1), cisplatin group (group 2), and cisplatin and melatonin group (group 3). While the rats in groups 2 and 3 were administered 5 mg/kg single dose of cisplatin via intra-peritoneal (IP) route, the rats in group 3 were started on melatonin (20 mg/kg IP) before cisplatin administration and continued during 3 consecutive days. Ovaries were removed one week after cisplatin administration in all groups. Blood samples were obtained before the rats were decapitated. Histological evaluation, follicle count, and classification were performed. TAp63 mRNA expression was evaluated using mRNA extraction and real-time polymerase chain reaction (PCR) method. Serum estradiol (E2) and anti-Mullerian hormone (AMH) values were measured with enzyme immune-assay technology.

Results: While primordial follicles were seen to decrease in group 2 as compared to group 1 (p=0.023), primordial follicle count was observed to be preserved significantly in melatonin group as compared to group 2 (p=0.047). Moreover, cisplatin-induced histo-pathological morphology was preserved in favor of normal histology in melatonin group. A significant difference was not observed between groups with regard to mean serum AMH and E2 values (p=0.102 and p=0.411, respectively). While TAp63 gene expression significantly increased in group 2 as compared to control group (p=0.001), we did not detect a statistically significant difference in cisplatin and melatonin group, although gene expression decreased (p=0.34).

Conclusions: We conclude that concurrent administration of melatonin and cisplatin may protect from ovarian damage.


Cisplatin, Melatonin, TAp63, Primordial follicle, Ovarian reserve

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