Biology subjects

Vaughan, O. R.

Publications and source records attributed to Vaughan, O. R..

4 recordsLinked to original sources

bioRxiv2025

HUMAN FETAL CIRCULATING FACTORS FROM PREGNANCIES COMPLICATED BY MATERNAL OBESITY INDUCE HYPERTROPHY IN NEONATAL RAT CARDIOMYOCYTES

AimObesity in pregnant women increases offspring cardiovascular risk and causes fetal cardiac dysfunction. The underpinning mechanisms remain unclear. We hypothesised that circulating factors in serum from fetuses of women with obesity induce pathological cardiomyocyte hypertrophy. MethodsPregnant women with obesity or healthy weight were recruited at term and provided umbilical cord serum and placentas, which were used for isolation of primary trophoblast cells. Primary cardiomyocytes were isolated from neonatal rats. ResultsCompared to serum-free medium, supplementing cardiomyocytes with umbilical cord serum increased their mRNA expression of atrial natriuretic factor (Anf) and brain natriuretic peptide (Bnp), hallmarks of pathological hypertrophy, but did not alter their size. Cord serum from women with obesity further upregulated cardiomyocyte Anf and Bnp, and increased the ratio of beta- to alpha-myosin heavy chain expression (Myh7:Myh6), compared to cord serum from healthy weight women. This effect was prevented by treating the cord serum with heat- freeze cycling and DNase or RNase digestion. Conditioned medium from trophoblast cells from women with obesity also increased cardiomyocyte Anf, Bnp and Myh7:Myh6 expression. MicroRNAs miR-142 and miR-17, which are associated with cardiac function, were increased in abundance in extracellular vesicles isolated from cord serum from women with obesity. However, miR-142-3p, miR-142-5p and miR-17-5p did not increase Anf, Bnp or Myh7:Myh6 expression when they were transfected into cardiomyocytes. ConclusionThe results show that human fetal circulating and placenta-derived factors induce hallmarks of pathological hypertrophy in cardiomyocytes and may mediate cardiac dysfunction in children of women with obesity.

physiology↗

bioRxiv2024

Low maternal plasma apelin in the second trimester is associated with adverse pregnancy outcome in severe, early-onset fetal growth restriction

ContextFetal growth restriction increases adverse pregnancy outcomes such as preterm birth and intrauterine fetal death. Apelin is a secreted peptide expressed in placental syncytiotrophoblast and downregulated in fetal growth restriction. ObjectivesWe tested the hypothesis that adverse pregnancy outcome is associated with low maternal plasma apelin at diagnosis of early-onset fetal growth restriction. MethodsPlasma samples and fetomaternal blood flow Doppler velocimetry measurements were obtained from pregnant women (n=59) at diagnosis of early-onset fetal growth restriction in the second trimester. Plasma apelin was determined by ELISA and pregnancy outcome was recorded. Placental gene expression was analysed after birth by qRT-PCR, compared to term placentas from women with late-onset fetal growth restriction or with appropriate-for-gestational age infants. ResultsAt diagnosis of early-onset fetal growth restriction, plasma apelin concentration was significantly lower in women who delivered extremely preterm (<28 weeks gestation) or had an intrauterine fetal death, compared to women who had a livebirth[≥]28 weeks (P<0.05). Plasma apelin correlated directly with uterine artery volume flow rate and inversely with pulsatility index. Placental gene expression of apelin, but not the apelin receptor or elabela, was lower in women with early-onset fetal growth restriction delivering preterm than in appropriate-for-gestational-age, term control women. ConclusionLow maternal circulating apelin during the second trimester is associated with impaired uteroplacental perfusion and subsequent adverse pregnancy outcome in severe, early-onset fetal growth restriction. Placental apelin deficiency may contribute mechanistically to the pathogenesis of early-onset fetal growth restriction.

physiology↗

bioRxiv2024

Adiponectin restores cholinergic vasodilation in resistance vessels from adult offspring exposed to maternal obesity in utero

Maternal obesity increases the risk of cardiovascular and metabolic disease in the offspring both during childhood and adult life. Pregnant women and mice with obesity have lower circulating levels of adiponectin (ADN) compared to lean controls. ADN is an adipokine involved in regulating energy metabolism, vascular function, and placental function. We hypothesized that offspring of obese mice have impaired resistance artery function, which can be prevented by restoration of normal circulating ADN levels in obese dams during late pregnancy. Adult female mice were fed either control or obesogenic diet and mated with control diet-fed males. Control dams received a continuous infusion of phosphate saline buffer (PBS) during late pregnancy whereas obese females received either PBS or ADN. After weaning, offspring were fed a control diet. Mesenteric arteries (MsA) were dissected from adult offspring and mounted in a wire myograph or fixed for histology. MsA responses to vasoconstrictors (phenylephrine and endothelin-1) were not different between infusion groups. However, the vasodilatory responses to acetylcholine were reduced in offspring from obese dams as compared to control-fed dams. ADN supplementation during pregnancy restored the cholinergic vasodilatory responses of resistance vessels in offspring from obese dams. These observations suggest that normalizing circulating adiponectin levels in pregnancies complicated by obesity prevents in utero programming of vascular dysfunction in the offspring.

developmental biology↗

bioRxiv2021

Maternal obesity causes fetal cardiac hypertrophy and alters adult offspring myocardial metabolism in mice

Obesity in pregnant women causes fetal cardiac dysfunction and increases offspring cardiovascular disease risk but its effect on myocardial metabolism is unknown. We hypothesised that maternal obesity alters fetal cardiac expression of metabolism-related genes and shifts offspring myocardial substrate preference from glucose towards lipids. Female mice were fed control or obesogenic diets before and during pregnancy. Fetal hearts were studied in late gestation (embryonic day, E18.5; term{approx}E21) and offspring were studied at 3, 6, 9 or 24 months postnatally. Maternal obesity increased heart weight and peroxisome proliferator activated receptor {gamma} (Pparg) expression in female and male fetuses and caused left ventricular diastolic dysfunction in the adult offspring. Cardiac dysfunction progressively worsened with age in female, not male, offspring of obese dams, compared to age-matched controls. In 6-month-old offspring, exposure to maternal obesity increased cardiac palmitoyl carnitine-supported mitochondrial respiration in males and reduced myocardial 18F-fluorodeoxyglucose uptake in females. Cardiac Pparg expression remained higher in adult offspring of obese than control dams and correlated with contractile and metabolic function. Maternal obesity did not affect cardiac palmitoyl carnitine respiration in females or 18F-fluorodeoxyglucose uptake in males, or alter cardiac 3H-oleic acid uptake, pyruvate respiration, lipid content or fatty acid/glucose transporter abundance in offspring of either sex. The results support our hypothesis and show that maternal obesity affects offspring cardiac metabolism in a sex-dependent manner. Persistent upregulation of Pparg expression in response to overnutrition in utero may mechanistically underpin programmed cardiac impairments and contribute to cardiovascular disease risk in children of women with obesity.

physiology↗