The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring.

Muh Geot Wong,Ibrahim Al-Odat,Anthony Gill,Sonia Saad,Sawiris Amgad,Yael Abreu-Villaça,Carol Pollock,Yik Lung Chan,Hui Chen

doi:10.1371/journal.pone.0103443

Muh Geot Wong, Ibrahim Al-Odat + Show 7 more

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https://doi.org/10.1371/journal.pone.0103443

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Abstract

This study aimed to investigate whether maternal cigarette smoke exposure can disrupt fetal kidney development by changing the expression of growth and transcription factors essential for renal development, and thereafter predispose the offspring to chronic kidney disease later in life. Female Balb/c mice (6 weeks) were exposed either to cigarette smoke or air under identical conditions, 6 weeks prior to mating, during gestation and during lactation. Male offspring were sacrificed at three time points, postnatal day (P)1, P20 (weaning age), and 13 weeks (mature age). Blood, urine, and kidneys were collected for analysis. At P1, the developmental genes fibroblast growth factor 2, glial cell-line derived neurotrophic factor and paired box 2 were upregulated at mRNA and protein levels; whilst fibroblast growth factor (FGF) 7 and FGF10 were downregulated. At P20, mRNA expression of FGF2, FGF10 and Wingless-type 4 was upregulated by maternal smoke exposure. These changes were normalised in adulthood. Nephron development was delayed, with fewer nephron numbers from P1 persisted to adulthood; while glomerular volume was increased at P20 but reduced in adulthood. Pro-inflammatory marker monocyte chemoatractant protein 1 (MCP1) was increased in the kidney by maternal smoke exposure. These changes were accompanied by an increased albumin/creatinine ratio in adulthood, suggesting reduced renal dysfunction. In conclusion maternal cigarette smoke exposure prior to and during pregnancy, as well as lactation leads to significant renal underdevelopment and functional abnormalities in adulthood. This study confirms the hypothesis that maternal smoking predisposes offspring to chronic kidney disorders.

Highlights

Many studies have established the association between maternal smoking and long-term health consequences in the offspring, including obesity, respiratory and cardiovascular diseases [1,2]
Maternal smoking is associated with intrauterine growth retardation (IUGR); while IUGR in turn, is associated with reduced nephron number in the offspring [3]
Intraperitoneal glucose tolerance test (IPGTT) IPGTT was performed at 12 weeks as previously described [20]

Summary

Introduction

Many studies have established the association between maternal smoking and long-term health consequences in the offspring, including obesity, respiratory and cardiovascular diseases [1,2]. Human research has shown that maternal smoking is closely linked to lower fetal kidney volumes during the second and third trimester, and lower birth weight [4]. Maternal smoking may impair renal function in the offspring once adulthood is reached [5,16,17], due to abnormal early development, including low numbers of nephrons and secondary hyperfiltration [5]. It is still unknown how maternal smoking is linked to an increased risk of developing chronic kidney disease in offspring [18]

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