Effects of changes in fat metabolism by particulate matter on endometrium and infertility.

Abstract

Particulate matter (PM) exposure has been increasingly linked to metabolic and reproductive disorders, yet the mechanisms through which PM-related metabolic alterations influence endometrial function remain incompletely understood. In this study, female C57BL/6 mice were fed a normocaloric diet or high-fat diet (HFD) with or without PM exposure for 12 weeks. Body weight, fertility outcomes, and molecular alterations were assessed in visceral adipose tissue (VAT) and endometrial tissue (EMT). In parallel, 3T3-L1 adipocytes were co-cultured with primary human endometrial cells to examine adipocyte-endometrial interactions in vitro. PM exposure was associated with attenuated overall weight gain but increased visceral adiposity and reduced fertility, particularly under HFD conditions. In both VAT and EMT, PM exposure was accompanied by increased expression of pro-inflammatory cytokines and elevated levels of p-NF-κB and p-c-jun. Alterations in adipokine profiles were observed, characterized by increased leptin and decreased adiponectin expression with PM exposure, particularly after the HFD. Hormone receptor expression displayed tissue-specific patterns, with higher AR and ER-α/ER-β ratios in VAT and opposite trends in EMT. Markers of cellular stress and apoptosis were also elevated in PM-exposed groups. In the co-culture model, PM exposure was associated with increased levels of p-Nrf2, p-ERK, and p-p38, together with altered leptin and adiponectin expression levels. Taken together, these findings suggest that PM exposure, particularly in the context of diet-induced obesity, may be associated with dysregulation of the adipose-endometrial crosstalk involving inflammation, oxidative stress-related signaling, and hormonal imbalance, which could contribute to adverse reproductive outcomes.