Maternal obesity: new placental paradigms unfolded. Issue 10 (October 2022)

• Record Type: Journal Article
• Authors: Brombach, Carolin; Tong, Wen; Giussani, Dino A.
• Is Part Of: Trends in molecular medicine. Volume 28:Issue 10(2022)
• Page Start: 823
• Page End: 835
• Publication Date: 2022-10
• Subjects: gestational obesity -- oxidative stress -- placental function -- inflammation -- ER stress -- unfolded protein response; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; Physiology, Pathological -- Periodicals; 572.8
• DOI: 10.1016/j.molmed.2022.05.013
• Languages: English
• ISSNs: 1471-4914

Abstract

Abstract : The prevalence of maternal obesity is increasing at an alarming rate, and is providing a major challenge for obstetric practice. Adverse effects on maternal and fetal health are mediated by complex interactions between metabolic, inflammatory, and oxidative stress signaling in the placenta. Endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR) are common downstream pathways of cell stress, and there is evidence that this conserved homeostatic response may be a key mediator in the pathogenesis of placental dysfunction. We summarize the current literature on the placental cellular and molecular changes that occur in obese women. A special focus is cast onto placental ER stress in obese pregnancy, which may provide a novel link for future investigation. Highlights: During maternal obesity, placental lipid accumulation, glycosylation end-products, and a shift in macrophage population contribute to chronic low-grade placental 'meta-inflammation'. Recent bioinformatic advances have highlighted mechanisms of placental lipid accumulation during maternal obesity, including fatty acid transporter expression, lipoprotein lipase activity, and alterations to mitochondrial metabolism. Inflammation and metabolic dysfunction increase placental oxidative and endoplasmic reticulum (ER) stress, and downstream activation of the placental unfolded protein response (UPR), all of which have been linked to complications of pregnancy, including fetal growth restriction, preeclampsia, and gestational diabetes. Human umbilical vein endothelial cells isolated from mothers with a high body mass index show evidence of ER stress, which can be recapitulated using high levels of glucose, palmitate, or acidosis in the culture medium. Recent evidence suggests that ER stress and UPR activation mediate adverse placental effects through alterations of nitric oxide metabolism and a shift in angiogenic balance.