Metabolic syndrome impairs endometrial functioning and early pregnancy: an in vivo study.

Abstract

Metabolic syndrome (MS) is increasingly associated with impaired reproductive health. This study aimed to assess the endometrial characteristics and reproductive outcomes of a female MS mouse model and evaluate metformin's therapeutic effects. Twenty-one-day-old female C57BL/6 mice were randomly divided into a high-fat diet group (N = 50) and a control group (N = 30) that received standard chow. After 11 weeks, a subset of HF mice (N = 25) was given oral metformin at 300 mg/kg/day, while the other ones continued on HF diet. After 15 weeks, mice were either sacrificed during estrus or mated and euthanized on day 7.5 of pregnancy (N = 15 per group). The estrous cycle, progesterone and estradiol levels, uterine morphology, endometrial cell proliferation, reproductive performance, and metformin's treatment effects were assessed. Mice on a high-fat diet developed MS, which was characterized by moderate glycemic dysregulation, increased cholesterol, insulin resistance, and central obesity. Experimental MS caused estrous cycle disruptions and increased serum progesterone levels, which were normalized by metformin. MS also affected endometrial histology, producing hyperplasia and altering cell proliferation, while metformin restored normal endometrial architecture by inhibiting cell proliferation. Additionally, MS impaired reproductive success by delaying coitus and reducing the ratio of implantation sites to corpora lutea, both of which were rectified by metformin. In conclusion, MS adversely affects reproductive function, but metformin offers improvement. Our findings highlight the need for further research on the impact of MS on reproduction and the exploration of treatments to enhance reproductive health in women with MS.