MitoQ supplementation prevent long-term impact of maternal smoking on renal development, oxidative stress and mitochondrial density in male mice offspring

Hui Chen,Sonia Saad,Brian G. Oliver,Rachana Santiyanont,Ayad G. Anwer,Razia Zakarya,Carol A. Pollock,Amgad A. Zaky,Yik Lung Chan,Suporn Sukjamnong,Long The Nguyen,Ewa Goldys

doi:10.1038/s41598-018-24949-0

Abstract

To investigate the effect of maternal MitoQ treatment on renal disorders caused by maternal cigarette smoke exposure (SE). We have demonstrated that maternal SE during pregnancy increases the risk of developing chronic kidney disease (CKD) in adult offspring. Mitochondrial oxidative damage contributes to the adverse effects of maternal smoking on renal disorders. MitoQ is a mitochondria-targeted antioxidant that has been shown to protect against oxidative damage-related pathologies in many diseases. Female Balb/c mice (8 weeks) were divided into Sham (exposed to air), SE (exposed to cigarette smoke) and SEMQ (exposed to cigarette smoke with MitoQ supplemented from mating) groups. Kidneys from the mothers were collected when the pups weaned and those from the offspring were collected at 13 weeks. Maternal MitoQ supplementation during gestation and lactation significantly reversed the adverse impact of maternal SE on offspring’s body weight, kidney mass and renal pathology. MitoQ administration also significantly reversed the impact of SE on the renal cellular mitochondrial density and renal total reactive oxygen species in both the mothers and their offspring in adulthood. Our results suggested that MitoQ supplementation can mitigate the adverse impact of maternal SE on offspring’s renal pathology, renal oxidative stress and mitochondrial density in mice offspring.

Highlights

It has been increasingly recognised that maternal programming during fetal development predisposes the offspring to future disease
We have previously demonstrated that maternal smoke exposure (SE) significantly reduced renal development in the male offspring and induced renal pathology in adulthood associated with increased oxidative stress and mitochondrial dysregulation[4,14]
We demonstrated that SE increased mitochondrial density and maternal renal DNA copy number and as a consequence increased total reactive oxygen species (ROS) levels in the mothers’ kidneys

Summary

Introduction

It has been increasingly recognised that maternal programming during fetal development predisposes the offspring to future disease. Maternal smoking imposes a significant adverse impact on fetal renal development that determines the future risk of chronic kidney disease (CKD) in adulthood[1]. Several studies indicated that maternal smoking is closely related to increased levels of oxidative stress in the mothers, infants and newborns[11,12], and reduced levels of the antioxidant enzymes superoxide dismutase (SOD) in the arteries of offspring from nicotine treated rats[13]. We demonstrated that oxidative stress and mitochondrial dysfunction are closely associated with the adverse effects of maternal smoking on the kidney pathology in the male offspring[14,15].

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