title: The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring.
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.
authors: School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia; Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.
authors: Ibrahim
authors: I
authors: Al-Odat
authors: School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia.
authors: Hui
authors: H
authors: Chen
authors: School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia.
authors: Yik Lung
authors: YL
authors: Chan
authors: Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.
authors: Sawiris
authors: S
authors: Amgad
authors: Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.
authors: Muh Geot
authors: MG
authors: Wong
authors: Anatomical pathology, Northern Clinical School, St Leonards, NSW, Australia.
authors: Anthony
authors: A
authors: Gill
authors: Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.
authors: Carol
authors: C
authors: Pollock
authors: Renal Medicine, Kolling Institute, St Leonards, NSW, Australia.
authors: Sonia
authors: S
authors: Saad
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D009399:Nephrons / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D012907:Smoking / Q000009:adverse effects*
chemical_list: D000418:Albumins; D018932:Chemokine CCL2; D003404:Creatinine