Maternal Diet-Induced Obesity Compromises Oxidative Stress Status and Angiogenesis in the Porcine Placenta by Upregulating Nox2 Expression

Abstract

Maternal obesity is associated with placental oxidative stress. However, the mechanism underlying this association remains poorly understood. In the present study, a gilt obesity model was developed by exposure to different energy diets and used to investigate the role of NADPH oxidase 2 (Nox2) in the placenta. Specifically, 99 gilts (Guangdong Small-ear Spotted pig) at day 60 of gestation were randomly assigned to one of the following three treatments: low-energy group (L, DE = 11.50 MJ/kg), medium-energy group (M, DE = 12.41 MJ/kg), and high-energy group (H, DE = 13.42 MJ/kg), with 11 replicate pens per treatment and 3 gilts per pen. At the start of the study, maternal body weight and backfat thickness were not significantly different in the three treatments. After the study, data indicated that the H group had higher body weight and backfat thickness gain for gilts during gestation and lower piglet birth weight compared with the other two groups. Additionally, the H group showed glucolipid metabolic disorders and increased triglyceride and nonesterified fatty acid contents in the placenta of gilts. Compared with the L group, the H group exhibited lower mitochondrial biogenesis and increased oxidative damage in the placenta. Importantly, increased mRNA expression and protein abundance of Nox2 were observed for the first time in H group placentae. Furthermore, compared with the L group, the H group showed a decrease in the density of placental vessels and the protein levels of vascular endothelial cadherin (VE-cadherin), vascular endothelial growth factor A (VEGF-A), and phosphorylation of vascular endothelial growth factor receptor 2 (p-VEGFR2) as well as the immunostaining intensity of platelet endothelial cell adhesion molecule-1 (CD31). Our findings suggest that maternal high-energy diet-induced obesity increases placental oxidative stress and decreases placental angiogenesis possibly through the upregulation of Nox2.

Maternal Overweight Downregulates MME (Neprilysin) in Feto-Placental Endothelial Cells and in Cord Blood

“…On the other hand, MME located at the cell membrane seems to participate in signaling events and has been shown to prevent FAK (focal adhesion kinase) activation and attenuates PKB (protein kinase B) signaling, causing reduced migration and angiogenesis (reviewed by Maguer-Satta et al [48]). Several reports describe distinct placental vascular structure as a result of obesity in human and animals, with either increased [49][50][51] or decreased [52][53][54] vascularity, suggesting that placental angiogenesis and vascular development is susceptible towards maternal metabolic and pro-inflammatory changes, but the effective result may depend on the specific situation, i.e., moderate vs. severe metabolic changes. In any event, altered angiogenesis in the placenta will generate distinct placental vascular structure and architecture, ultimately affecting hemodynamics.…”

Placentae for Low Birth Weight Piglets Are Vulnerable to Oxidative Stress, Mitochondrial Dysfunction, and Impaired Angiogenesis

“…Placental tissues fixed in 4% paraformaldehyde were paraffin-embedded and sectioned at 5 μm thickness for platelet endothelial cell adhesion molecule-1 (CD31) immunofluorescence. The method was performed as described previously [33].…”

Sex Differences in Placental Protein Expression and Efficiency in a Rat Model of Fetal Programming Induced by Maternal Undernutrition

“…Poor vascularization of the placenta has been associated with pregnancy complications, such as maternal obesity, preeclampsia, and FGR. Reduced angiogenesis has also been detected in placenta from rats exposed to toxic substances [ 36 ] and in obesity models [ 37 ], showing reduced gene expression of VEGF and other angiogenic factors. However, these studies did not evaluate sex differences.…”