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

Al-Odat I1, Chen H2, Chan YL2, Amgad S3, Wong MG3, Gill A4, Pollock C3, Saad S3.

PLoS One. 2014 Jul 24;9(7):e103443.

 

1School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia; Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.

2School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia.and

3Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.

4Anatomical pathology, Northern Clinical School, St Leonards, NSW, Australia.

 

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.

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