• Improvement of ovarian tissue in rats with polycystic ovary syndrome treated with the anti diabetic drug Empagliflozin
  • Marzieh Jokar,1 Farangis Ghasemi ,2,* Hosein Kargar Jahromy,3
    1. Department of Biology, Jahrom Branch, Islamic Azad University, Jahrom, Iran
    3. Research Center for Noncommunicable Diseases, Jahrom University of Medical Sciences, Jahrom, Iran


  • Introduction: Polycystic ovary syndrome (PCOS) is one of the endocrine disorders in women of reproductive age, which has no specific treatment due to its multifactorial nature. Therefore, it is important to provide new treatment solutions. Considering the incidence of insulin resistance and blood glucose increase in polycystic ovary syndrome on one hand and the anti-diabetic properties of empagliflozin on the other hand, the effect of this drug in the treatment of PCOS complications was investigated.
  • Methods: Forty female rats (Wistar) with 200-220g weight were selected and divided into 5 equal groups. All rats, except the control group (healthy rats), became PCOS with daily oral administration of 1 mg/kg/bw of letrozole solution. Then they were divided into Control groups (healthy rats), Sham 1 (PCO without treatment), Sham 2 (PCOS rats treated with 500mg/kg/bw metformin), and two groups treated with doses of 30 and 50 (mg/kg/bw) of Empagliflozin solution. After 60 days of treatment, according to the principles of working with animals, all rats were anesthetized and blood was taken from them. Immediately, the ovarian tissue was removed from the body, fixed in a 7% formalin solution, and transferred to the laboratory to prepare tissue sections by the standard stereological method. The slides were prepared and photographed with a microscope equipped with a camera. The thickness of the theca, the diameter of the ovum, and the corpus luteum were measured using Streolite software, and the number of follicles was counted. The resulting data (Mean ± SD) were analyzed with SPSS version 20 software and ANOVA, and the groups were compared with Tukey tests.
  • Results: The findings of this research showed that the use of metformin and empagliflozin in treated groups decrease blood glucose, body mass, luteinizing hormone, and testosterone, and increase follicle stimulating hormone and progesterone in comparison to PCO rats without treatment (Sham 1) significantly (p<0.5). Also, the adverse changes in ovarian tissue caused by PCO induction include a decrease in the diameter and number of corpus luteum, a decrease in the diameter of the ovum, the occupation of a larger volume of the ovary by cystic and atretic follicles, and a greater thickness of the theca, were improved especially in rats consuming a higher dose of empagliflozin. The results showed a significant increase in the average number of single-layered follicles and a significant decrease in the number of antral follicles and Graafian follicles in the PCO group compared to the control group, which was significantly compensated in the groups taking metformin and especially the higher dose of empagliflozin. They reached the level of the Control group. The mean number of primary follicles was not significantly different between the studied groups, but there was a significant decrease in the mean of corpus luteum in the PCO group compared to the control group (p<0.001), it was adjusted by taking both drugs. Cystic and atretic follicles were reduced by treatment with metformin, and empagliflozin especially at higher doses (p<0.001) and (p<0.001) in the treated groups.
  • Conclusion: Empagliflozin has significantly improved the adverse changes caused by PCOS in ovarian tissue and the number of follicles with a similar effect to metformin. The more effect of the higher dose of empagliflozin compared to a lower dose and metformin shows the dependence of the drug effect on the appropriate dose. With more research on this drug, it may be a good option in the treatment of PCOS.
  • Keywords: Empagliflozin, Body mass, Follicle graph, Blood sugar, Theca