Obese women often have certain degree of reproductive dysfunction with infertility. Although the clinical impact of obesity on female infertility has been extensively studied, the effective and targeted treatment is still lacking. Melanocor tin-4-receptor knock-out (MC4R KO) mouse is an over-eating obese model with hyperphagia, hyperinsulinemia, reduced growth hormone (GH), and insulin resistance. Dapaglifloz in improved the metabolic and hormonal parameters in MC4R KO mice. MC4R KO female mice were treated with dapagliflozin for 14 weeks from 14-week age. Age-ma tched WT littermates and non-treated MC4R KO mice were used as control groups. Food intake was measured daily. Body weight was measured twice a week. Estrous cycles, G H, and luteinizing hormone (LH) profiles were measured. Selected tissues were colle cted at the end of experiments for gene expression profiles and hematoxylin--eosin s taining. Regularity and mode of hormonal profiles were restored by the dapagliflozin trea tment. Estrous cycle was partially normalized, number of CL was significantly increas ed, and the expression of Kiss1 and Gnrh1 in the hypothalamus and LH in the pituitary was markedly increased by the dapagliflozin treatment. It is conclsuded that dapaglifloz in may recover LH and GH profiles partially through modification of relevant gene expressi on in the hypothalamus and pituitary, and result in an improved ovulation rate in obese mouse model. Dapagliflozin may therefore improve fertility in obese patients. [ABSTRACT FROM AUTHOR]