The effects of metformin treatment on the ovaries and uterus of offspring

Abstract

Objective: The aim of this study is to investigate the effects of metformin treatment at different dosage levels on the ovaries and uteruses of rat offspring in the course of the intrauterine period.

Methods: Saline, metformin (100 mg/kg/day), and metformin (200 mg/kg/day) were administered via oral gavage between the 6th and 15th days of gestation to the 9 pregnant rats (n = 3/group). After birth, 5 female offspring were separated from each group and perfused on the 60th day of postnatal development. The cortex and medulla volumes of the ovaries, the thicknesses of epithelium and endometrium of the uteruses and the total oocyte number density were estimated. In addition, the estradiol levels in blood samples were measured by the ELISA method.

Results: There were no statistically significant differences among the groups regarding the number of oocytes, the volumes of ovarian cortex, medulla, primary and secondary follicles (p > .05). In comparison with the control group, the volume of the tertiary follicle, the thickness of the uterus epithelium, and the estradiol level were significantly decreased in Metformin 200 group (p < .05).

Conclusions: The gestational exposure to high dose metformin may result in decreased estradiol production and subsequently decreased endometrial thickness of offspring rats.

Keywords: Metformin; ovary; pregnancy; stereology; uterus.