Inflammation-Associated Transcriptional Remodeling of Antioxidant and Stress Signaling Pathways in First-Trimester Placenta in Maternal Overweight and Obesity.

The first trimester (FT) of pregnancy is characterized by rapid placental growth and differentiation, rendering this period sensitive to maternal metabolic influences. Maternal obesity is associated with chronic low-grade inflammation and altered redox homeostasis with implications in later cardiometabolic risk in offspring, yet its impact on early placental oxidative stress remains unclear. Here, we investigated whether maternal overweight and obesity are associated with oxidative lipid and protein damage and altered expression of antioxidant enzymes and stress signaling pathways. Placental tissue from lean (BMI < 25 kg/m2), overweight (BMI ≥ 25 kg/m2) and obese (BMI ≥ 30 kg/m2) non-smoking women (5-12 weeks' gestation) was analyzed. Oxidative damage was assessed by immunoblotting for 4-hydroxynonenal and 3-nitrotyrosine, and antioxidant and stress-related transcripts were quantified using targeted mRNA arrays. Explants were exposed to increased oxygen tension or TNF-α to evaluate transcriptional responsiveness. No differences in oxidative lipid or protein modifications were detected between groups. In contrast, overweight and obesity were associated with reduced expression of selected antioxidant enzymes and transcriptional remodeling of MAPK-related genes. These changes correlated with IL6 expression but not with oxidative damage markers. Collectively, maternal overweight and obesity are linked to inflammation-associated transcriptional adaptation in FT placenta without detectable oxidative injury.