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

In brief This study demonstrated that metabolic syndrome (MetS) in mice disrupts the estrous cycle, increases progesterone levels and alters the endometrial structure, resulting in impaired reproductive success. Treatment with metformin effectively reversed these effects, restoring hormonal balance and normal endometrial architecture and improving reproductive outcomes. Abstract MetS is increasingly associated with impaired reproductive health. This study aimed to assess the endometrial characteristics and reproductive outcomes of a female MetS mouse model and evaluate metformin’s therapeutic effects. Twenty-one-day-old female C57BL/6 mice were randomly divided into a high-fat (HF) 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 the HF diet developed MetS, which was characterized by moderate glycemic dysregulation, increased cholesterol, insulin resistance and central obesity. Experimental MetS caused estrous cycle disruptions and increased serum progesterone levels, which were normalized by metformin. MetS also affected endometrial histology, producing hyperplasia and altering cell proliferation, while metformin restored the normal endometrial architecture by inhibiting cell proliferation. In addition, MetS impaired the reproductive success by delaying coitus and reducing the ratio of implantation sites to corpora lutea, both of which were rectified by metformin. In conclusion, MetS adversely affects reproductive function, but metformin offers improvement. Our findings highlight the need for further research on the impact of MetS on reproduction and the exploration of treatments to enhance reproductive health in women with MetS.