Maternal obesity reduces placental autophagy marker expression in uncomplicated pregnancies

Abstract

Aim Obesity has been associated with changes in autophagy and its increasing prevalence among pregnant women is implicated in higher rates of placental‐mediated complications of pregnancy such as pre‐eclampsia and intrauterine growth restriction. Autophagy is involved in normal placentation, thus changes in autophagy may lead to impaired placental function and development. The aim of this study was to investigate the connection between obesity and autophagy in the placenta in otherwise uncomplicated pregnancies. Methods Immunohistochemistry and western blot analysis were done on placental and omental samples from obese (body mass index [BMI] ≥30 kg/m2) and normal weight (BMI <25 kg/m2) pregnant women with singleton pregnancies undergoing planned Caesarean delivery without labor at term. Samples were analyzed for autophagic markers LC3B and p62 in the peripheral, middle and central regions of the placenta and in omental adipocytes, milky spots and vasculature. Results As pre‐pregnancy BMI increased, there was an increase in both placental and fetal weight as well as decreased levels of LC3B in the central region of the placenta (P = 0.0046). Within the obese patient group, LC3B levels were significantly decreased in the placentas of male fetuses compared to females (P < 0.0001). Adipocytes, compared to milky spots and vasculature, had lower levels of p62 (P = 0.0127) and LC3B (P = 0.003) in obese omenta and lower levels of LC3B in control omenta (P = 0.0071). Conclusion Obesity leads to reduced placental autophagy in uncomplicated pregnancies; thus, changes in autophagy may be involved in the underlying mechanisms of obesity‐related placental diseases of pregnancy.

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.…”

“…101 In a recent study by Cohen et al, 105 maternal obesity reduced placental autophagy through quantification of autophagy-related proteins LC3B and p62 from placentas from pregnancies complicated by obesity compared with healthy weight counterparts. However, hypoxia, a known inducer of autophagy, 106e108 was increased in placentas of patients with obesity and was accompanied by a concomitant increase in placental markers of autophagy in Gohir et al, 56 albeit by messenger RNA (mRNA) expression and not protein expression as reported in the study by Cohen, et al 105 The genes used as autophagy markers were also different between the 2 studies, with Vsp15 and Vps34 used in the study by Gohir et al 56 and LC3B and p62 in the study by Cohen et al, 105 which may account for differences between the 2 studies. Furthering the case for obesity-inducing defects in autophagy, Hong et al 109 found that the addition of palmitate to human extravillous trophoblasts induced protein aggregates, increased the association of p62 with these protein aggregates, and increased LC3B levels in the cell.…”

Maternal obesity and offspring health: Adapting metabolic changes through autophagy and mitophagy

“…Noticeably, emerging findings have suggested a vital role for mitochondrial dysregulation in the ever‐rising risk of metabolic diseases in offspring or later generations following intrauterine overnutrition 18,19 . In particular, impaired autophagy/mitophagy and metabolic disturbances recognized under maternal obesity negatively impact fetal development to certain degrees 20 . In this review, we aim to provide an update on the metabolic disorders in fetal development and postnatal health issues evoked by maternal obesity and discuss the possible contribution of changes in autophagy/mitophagy in the etiology of various metabolic diseases.…”

“…18,19 In particular, impaired autophagy/mitophagy and metabolic disturbances recognized under maternal obesity negatively impact fetal development to certain degrees. 20 In this review, we aim to provide an update on the metabolic disorders in fetal development and postnatal health issues evoked by maternal obesity and discuss the possible contribution of changes in autophagy/mitophagy in the etiology of various metabolic diseases. Relevant mechanisms and potential therapeutic strategies targeting autophagy/mitophagy and metabolic disturbances will also be addressed for maternal obesity.…”

The Presence of the Autophagic Markers LC3B and Sequestosome 1/p62 in the Hydatidiform Mole

“…It seems to be increased in placentas from preeclampsia (8,9) and fetal growth restriction pregnancies (5,10), and to contribute to spontaneous abortion when this mechanism is insufficient (7,11). It has also been shown to be reduced in placentas from obese women (12) and to be increased in placentas of newborns with neonatal encephalopathy (13).…”