Oxidative Stress Impairs Fatty Acid Oxidation and Mitochondrial Function in the Term Placenta

Abstract

Placental fatty acid oxidation (FAO) is impaired and lipid storage is increased in pregnancy states associated with chronic oxidative stress. The effect of acute oxidative stress, as seen in pregnancies complicated with asthma, on placental lipid metabolism is unknown. We hypothesized that induction of acute oxidative stress would decrease FAO and increase esterification. We assessed [3H]-palmitate oxidation and esterification in term placental explants from lean women after exposure to hydrogen peroxide (H2O2) for 4 hours. Fatty acid oxidation decreased 16% and 24% in placental explants exposed to 200 ( P = .02) and 400 µM H2O2 ( P = .01), respectively. Esterification was not altered with H2O2 exposure. Neither messenger RNA nor protein expression of key genes involved in FAO (eg, peroxisome proliferator-activated receptor α, carnitine palmitoyl transferase 1b) were altered. Adenosine triphosphate (ATP) levels decreased with induction of oxidative stress, without increasing cytotoxicity. Acute oxidative stress decreased FAO and ATP production in the term placenta without altering fatty acid esterification. As decreases in placental FAO and ATP production are associated with impaired fetal growth, pregnancies exposed to acute oxidative stress may be at risk for fetal growth restriction.

Associations among perfluorooctanesulfonic/perfluorooctanoic acid levels, nuclear receptor gene polymorphisms, and lipid levels in pregnant women in the Hokkaido study

“…The PPARGC1A rs8192678 (G>A, Gly482Ser; exon 8) GG genotype demonstrated higher sports performance, athletic ability 56 , endurance performance ability 57 , hepatic adenosine triphosphate (ATP) levels 58 , PPARGC1A gene expression 54 , lower risk of polycystic ovarian syndrome 59 , nonalcoholic fatty acid disease 30 , type 2 diabetes mellitus 60 , 61 , and obesity 62 . Increased ATP levels decreased with oxidative stress induction, and acute oxidative stress decreased placental FA oxidation 63 . Other specific PPARG genotype modified serum lipid levels via PPARG2 expression in adipose tissue 64 .…”

The Influence of Obesity and Associated Fatty Acids on Placental Inflammation

“…Although oxidative stress induced by fatty acids was largely consistent, mitochondrial function as assessed by mitochondrial DNA was less consistent, with studies finding conflicting results (possibly explained by different mitochondrial DNA replicationassociated mRNAs assessed). 93,98,134 Autophagy was similarly conflicted, with some studies finding increases in autophagy markers, 56 whereas others found defects in markers or function, 105,109 which may be explained by studies quantifying different autophagy-associated mRNAs. The study that found autophagosome-lysosome fusion defects also found increases in autophagy-associated mRNAs and autophagy defects, 109 which may provide the best answer to this question of whether autophagy may be increased when querying the mRNA level, but functional studies can still ultimately find persistent defects in autophagy.…”

Article A Genome-Wide Association Study To Identify Candidate Genes for Metabolic Disorders in Offspring by In Vitro Fertilization

“…Since fatty acids are important energy source for oocyte and embryo development, their abnormal metabolism can affect the normal development of embryo [58] . Oxidative stress leads to impaired embryo fatty acid oxidation (FAO) and increased lipid storage and impairs embryo fatty acid oxidation and mitochondrial function [59] . In addition, oocyte quality is a critical factor determining embryo quality, such as high lipid levels and ROS increase, resulting in poor oocyte and embryo development quality.…”