Placental Volume, Vascularization, and Epigenetic Modifications in Obesity and Gestational Diabetes: A 3-D Ultrasound and Molecular Analysis

Kolcsar, Balint and Kemeny, Kata Kira and Kozinszky, Zoltan and Ducza, Eszter and Surányi, Andrea (2025) Placental Volume, Vascularization, and Epigenetic Modifications in Obesity and Gestational Diabetes: A 3-D Ultrasound and Molecular Analysis. LIFE-BASEL, 15 (11). No. 1691. ISSN 2075-1729

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Abstract

Background: Obesity and gestational diabetes mellitus (GDM) are the most common metabolic conditions that have an unfavorable impact on maternal and fetal health. Maternal obesity and GDM are often associated with placental dysfunction and structural alterations. The apelin receptor (APLNR), vascular endothelial growth factor (VEGF), leptin, and DNA methylation play crucial roles in placental function. We aimed to investigate the placental volume and vascularization, and to determine the changes in these markers in obese and GDM mothers. Material and Methods: In our study, we investigated the human placenta (n = 48) at term. The placental structural analyses on volume and vascularization were conducted using three-dimensional ultrasound before labor. Placental APLNR expression was determined using RT-PCR, and leptin and VEGF concentrations using ELISA in placental tissues. Global DNA methylation was measured using colometric assay. Results: The age of GDM mothers was significantly higher than that of normal and obese mothers. The gestation length of GDM mothers was significantly shorter than that of normal and obese mothers. The placental volume was significantly higher in obese and GDM cases compared with normal cases. Vascularization indices (VI, FI, VFI) were significantly depressed in GDM and obesity. In the case of biomarker studies, APLNR, leptin, and VEGF showed similar decreases in obese and GDM placentas. Based on our results, the effect of GDM, not obesity, was more pronounced for these biomarkers. VEGF reduction correlates with three-dimensional placental vascularity studies. The DNA methylation was significantly elevated in both GDM and obese placental samples, while the GDM effect was more pronounced. Conclusions: This study is the first to demonstrate structural alterations of the placenta using placental tissue biomarkers in obesity and gestational diabetes mellitus (GDM). We found that both GDM and obesity affect placental volume and vascularity, as indicated by reduced leptin and VEGF levels, presumably mediated by epigenetic effects. Our findings may provide a novel therapeutic target for improving abnormal placental function caused by GDM and obesity.

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