Perinatal Oxidative Stress May Affect Fetal Ghrelin Levels in Humans.

Zhong-Cheng Luo,Emile Levy,Lin Xiao,Pierre Julien,Francois Audibert,Anne Monique Nuyt,Jean-François Bilodeau,Carole Garofalo,William D Fraser

doi:10.1038/srep17881

Abstract

In vitro cell model studies have shown that oxidative stress may affect beta-cell function. It is unknown whether oxidative stress may affect metabolic health in human fetuses/newborns. In a singleton pregnancy cohort (n = 248), we studied maternal (24–28 weeks gestation) and cord plasma biomarkers of oxidative stress [malondialdehyde (MDA), F2-isoprostanes] in relation to fetal metabolic health biomarkers including cord plasma glucose-to-insulin ratio (an indicator of insulin sensitivity), proinsulin-to-insulin ratio (an indicator of beta-cell function), insulin, IGF-I, IGF-II, leptin, adiponectin and ghrelin concentrations. Strong positive correlations were observed between maternal and cord plasma biomarkers of oxidative stress (r = 0.33 for MDA, r = 0.74 for total F2-isoprostanes, all p < 0.0001). Adjusting for gestational age at blood sampling, cord plasma ghrelin concentrations were consistently negatively correlated to oxidative stress biomarkers in maternal (r = −0.32, p < 0.0001 for MDA; r = −0.31, p < 0.0001 for F2-isoprostanes) or cord plasma (r = −0.13, p = 0.04 for MDA; r = −0.32, p < 0.0001 for F2-isoprostanes). Other fetal metabolic health biomarkers were not correlated to oxidative stress. Adjusting for maternal and pregnancy characteristics, similar associations were observed. Our study provides the first preliminary evidence suggesting that oxidative stress may affect fetal ghrelin levels in humans. The implications in developmental “programming” the vulnerability to metabolic syndrome related disorders remain to be elucidated.

Highlights

Consistent evidence suggests that the perinatal period is a critical developmental time window in “programming” future risk of metabolic syndrome [obesity, impaired glucose tolerance, elevated blood pressure, high serum triglycerides and low serum high-density lipoprotein (HDL) levels] and related disorders[1,2] How this vulnerability is developed during fetal life remains unclear
Descriptive statistics on other biomarkers in this cohort have been reported in previous works[12,17,18], and are not presented here
Gestational age at birth was positively correlated to cord plasma leptin and adiponectin (r = 0.19, p = 0.0025) concentrations, but negatively correlated to cord plasma insulin-like growth factor I (IGF-I) (r = − 0.22, p = 0.0001) concentrations

Summary

Introduction

Consistent evidence suggests that the perinatal period is a critical developmental time window in “programming” future risk of metabolic syndrome [obesity, impaired glucose tolerance, elevated blood pressure, high serum triglycerides and low serum high-density lipoprotein (HDL) levels] and related disorders (e.g. type 2 diabetes)[1,2] How this vulnerability is developed during fetal life remains unclear. There is a lack of data on whether oxidative stress may affect metabolic health biomarkers in human fetuses/newborns. The present study sought to explore the hypothesis that perinatal oxidative stress may affect circulating levels of metabolic health biomarkers as related to fetal growth (insulin, IGF I and IGF II), insulin sensitivity, beta-cell function and energy regulation (leptin, adiponectin, ghrelin) in human fetuses/newborns. Ghrelin is mainly secreted by the pancreas during fetal life, rather than the fundus of the stomach in adult humans[11]. It is unknown whether this “pancreatic” fetal hormone is related to perinatal oxidative stress

Methods

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Discussion

Conclusion