The effects of melatonin and metformin on histological characteristics of the ovary and uterus in letrozole-induced polycystic ovarian syndrome mice: A stereological study

Background: Polycystic ovarian syndrome (PCOS) with anovulation, hyperandrogenism, ovarian and uterine histological changes, menstrual irregularities, etc. signs is an infertility type. It seems that melatonin and metformin can improve these abnormalities. Objective: To evaluate the effects of melatonin and metformin on the ovary and uterus in PCOS-induced mice using stereological methods. Materials and Methods: ۷۲ adult female BALB/c mice (۸-wk-old, ۲۰-۳۰ gr) were randomly divided into control (distilled water, gavage), PCOS (۹۰ µg/kg letrozole, gavage), PCOS+metformin (۵۰۰ mg/kg, gavage), PCOS+melatonin (۱۰ mg/kg, intraperitoneal injection), and PCOS+melatonin control (۰.۵% ethanol saline) groups (n = ۱۲/each). Another PCOS group was kept for a month to ensure that PCOS features remained. Finally, a stereological evaluation of the uterus and ovary was carried out, and vaginal cytology and serum testosterone levels were assessed. Results: PCOS mice treated with metformin and melatonin had lower testosterone levels, body weight, and more regular estrus cycles than the PCOS group (p ≤ ۰.۰۰۱). A significant decrease in conglomerate and daughter gland numbers, and primary, secondary, atretic, and cystic follicles numbers with a significant increase in primordial and Graafian follicles, and corpus luteum numbers (p ≤ ۰.۰۰۱) was seen in these treated mice. Also, endometrial vessels' volume and length significantly increased, but ovarian, endometrial, myometrial, stromal, and glands volume, and endometrial and myometrial thickness dramatically declined (p ≤ ۰.۰۰۱). Conclusion: It appears that metformin and melatonin could restore the PCOS phenotype including estrus cycle irregularity, high testosterone level, and ovarian and uterine micromorphology to the control levels. However, the ۲ treatments had similar effects on the examined parameters.

کلیدواژه ها:

Polycystic ovarian syndrome ، Melatonin ، Metformin ، Ovary ، Uterus ، Mice ، Stereology. ، سندرم تخمدان پلی­کیستیک ، ملاتونین ، متفورمین ، تخمدان ، رحم ، موش ، استریولوژی.