Semaglutide Improves Fertility in Obese Mice by Reducing Ovarian Inflammation and Oxidative Stress

Female C57BL mice were divided into three groups: normal diet (NC), high-fat diet (HFD), and high-fat diet + semaglutide (HS). Assessments included body weight/composition, glucose/insulin/pyruvate tolerance, systemic and ovarian inflammatory cytokines, reproductive hormones, ovarian gene expression (SIRT1, SIRT6, FOXO1, FOXO3a, NRF1, IRS1, iNOS, eNOS, p27 KIP1, PTEN), ovarian histopathology, oocyte mitochondrial function, DNA damage, lipid/ROS levels, and fertility testing.

Obesity-related infertility affects millions of women worldwide and is becoming more common. This study shows semaglutide can improve fertility by directly addressing the ovarian damage caused by obesity — not just through weight loss but through specific anti-inflammatory and anti-oxidative mechanisms. This adds a fertility-related benefit to the already extensive list of semaglutide's therapeutic effects.

This study adds reproductive health to the expanding list of organ systems benefited by GLP-1 receptor agonists. The finding that semaglutide works through the SIRT pathway — proteins associated with longevity and cellular protection — connects peptide therapeutics with fundamental cellular defense mechanisms. As GLP-1 drugs become widely used for weight management, understanding their reproductive effects is critical for the millions of reproductive-age women taking these medications.

This was a mouse study using diet-induced obesity, which may not fully replicate human obesity-related infertility. It's unclear whether semaglutide's reproductive benefits come from weight loss alone or from direct ovarian effects independent of weight. The study did not assess whether semaglutide is safe to continue during pregnancy in mice. Specific semaglutide dosing was not detailed in the abstract.