Obesity Reduces Endometrial Receptivity by Downregulating the Ob-Rb/STAT-3 Signaling Pathway in Women and Female Mice

Area of Science:

• Reproductive Endocrinology
• Obesity Research
• Molecular Biology

Background:

• Obesity is linked to infertility, but the underlying mechanisms affecting endometrial receptivity are not fully understood.
• Leptin levels are elevated in obesity, and its receptor (Ob-Rb) is present in the human endometrium.
• The specific role of leptin signaling in obesity-related endometrial dysfunction requires further investigation.

Purpose of the Study:

• To investigate the mechanism by which obesity impairs endometrial receptivity via the leptin signaling pathway.
• To compare leptin receptor (Ob-Rb) and STAT-3 signaling in the endometrium of normal-weight, overweight, and obese women.
• To evaluate the impact of leptin signaling modulation on endometrial receptivity in diet-induced obesity (DIO) mouse models.

Main Methods:

• Human study: Measured serum leptin, Ob-Rb, pSTAT-3, LIF, and VEGF in women across weight categories.
• Animal study: Utilized DIO mice, leptin resensitization models, and Ob-Rb inhibitor models.
• Assessed endometrial receptivity markers and pregnancy outcomes in experimental mouse models.

Main Results:

• Obese women and DIO mice exhibited higher leptin levels but decreased Ob-Rb, pSTAT-3, LIF, and VEGF expression.
• DIO mice showed reduced pregnancy rates and blastocyst numbers compared to normal-weight controls.
• Leptin resensitization in DIO mice improved Ob-Rb/STAT-3 signaling and endometrial receptivity markers.

Conclusions:

• Obesity-induced dysfunction of the Ob-Rb/STAT-3 signaling pathway is a key factor in impaired endometrial receptivity.
• Leptin resistance and Ob-Rb/STAT-3 signaling are potential therapeutic targets for infertility associated with obesity.
• Weight loss-induced leptin resensitization offers a potential strategy to partially reverse obesity-related infertility.