Abstract
Abstract
Obesity is a major risk factor for subfertility and poor reproductive outcomes in women; however, the impact of elevated body mass index (BMI) on the ovarian immune microenvironment remains unclear. We investigated BMI-associated molecular and functional changes in follicular fluid (FF) and granulosa cells (GCs) obtained from women undergoing assisted reproductive technology and stratified into low-BMI (< 22.9 kg/m²) and high-BMI (≥ 25 kg/m²) groups. RNA sequencing revealed that high-BMI GCs exhibited suppression of immune-related pathways. Chemokine (C-C motif) ligand 3 (CCL3) was significantly reduced in high-BMI GCs and inversely correlated with BMI at both mRNA and protein levels in FF. Functionally, FF from women with high BMI showed markedly diminished chemotactic activity toward THP-1 monocytes in a chemotaxis assay, indicating impaired immune cell recruitment capacity of the follicular milieu. In addition, CYP27A1, a key regulator of cholesterol and oxysterol metabolism, was selectively downregulated in high-BMI GCs. Together, these results indicate that elevated BMI is associated with suppression of chemokine signaling and lipid-associated metabolic pathways in human GCs. Our findings provide functional evidence that obesity compromises immune cell recruitment within the ovarian follicular microenvironment, thereby offering a mechanistic link between metabolic status and impaired follicular homeostasis in women with increased BMI.