The Ameliorative Effects of L-Carnitine on Decidualization in High-Fat Diet-Induced Rats and Human Endometrial Stromal Cells
Description
Objective: Previous evidence indicates that obesity disrupts endometrial decidualization through inflammatory and oxidative stress pathways. L-carnitine (LC), a mitochondrial fatty acid oxidation enhancer and antioxidant, has shown potential in improving reproductive outcomes. We aimed to investigate whether LC ameliorates obesity-induced decidualization impairment and its mechanism. Methods: In this study, obese female rats induced by a high-fat diet (HFD) were administered various concentrations of LC at doses of 135 mg, 400 mg, and 1200 mg/kg/day via oral gavage, with metformin serving as the control. After pairing with male rats, the animals were sacrificed on gestational day 7, and uterine specimens were collected for subsequent analysis. Additionally, palmitic acid (PA) was used as a high-fat cell inducer in human endometrial stromal cells (hESCs), followed by supplementation with LC to investigate its effects on decidualization processes. Results: Compared with metformin, the administration of LC (400 mg/kg) restored the number of embryo implantations and decidualization in vivo. LC was found to increase the expression of sirtuin 1 (SIRT1) and Forkhead box class O 1 (FOXO1), while simultaneously decreasing the levels of acetyl-FOXO1. In vitro, LC reversed the PA-induced suppression of decidualization markers, restored mitochondrial polarization, and reduced oxidative stress. Notably, LC treatment restored SIRT1/FOXO1 signaling pathways and enhanced the expression of the progesterone receptor (PR) both in vivo and in vitro. Conclusion: LC ameliorates impaired endometrial decidualization in HFD-fed rats and hESCs via the SIRT1/FOXO1/PR pathway.