 This research found that Epirubicin, a commonly used chemotherapy drug for breast cancer patients, significantly reduced body weight, ovary and uterus weight, and pup number in mice. Melatonin, which is resistant to oxidation, significantly reduced these damages and prevented Epirubicin-induced decrease in E2 and progesterone and loss of follicles. Mechanism studies showed that melatonin reduced the levels of pro-apoptotic genes P53, caspase 3, and caspase 9 while at pregulating anti-apoptotic factors BCl2 and BCl2L1, and antioxidant gene superoxide dismutase 1 and catalase. Melatonin also reduced reactive oxygen species, ROS, and transcription of caspase 12 and chomp, which is vital in endoplasmic reticulum stress-mediated apoptosis. These results suggest that melatonin protects against Epirubicin-induced ovarian damage by reducing ROS-induced endoplasmic reticulum stress. Therefore, melatonin has therapeutic potential for the protection of ovarian function and preservation of fertility during chemotherapy. This article was authored by Nai Chen Wang, Hualei, Yunching Zhechu, and others. We are article.tv. Links in the description below.