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.

摘要

目的:探讨不同剂量二甲双胍治疗对宫内妊娠大鼠子代卵巢和子宫的影响。

方法:9只妊娠大鼠(n = 3/组)于妊娠第6 - 15天灌胃生理盐水、二甲双胍(100 mg/kg/day)、二甲双胍(200 mg/kg/day)。出生后, 每组分出5只雌性后代, 于出生后60天后灌胃。测定卵巢皮质和髓质体积, 子宫上皮和子宫内膜厚度及卵母细胞总数密度。另外, 采用ELISA法测定血中雌二醇水平。

结果:两组间卵母细胞数、卵巢皮质、髓质、初级卵泡、次级卵泡体积差异无统计学意义(p > .05)。与对照组相比, 二甲双胍200组三级卵泡体积、子宫上皮厚度及雌二醇水平明显降低(p<0 .05)。

结论:妊娠期高剂量二甲双胍暴露可能导致子代大鼠雌二醇的产生减少, 进而降低子宫内膜厚度。

Keywords:

• Metformin
• ovary
• pregnancy
• stereology
• uterus

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Disclosure statement

No potential conflict of interest was reported by the author(s).