PMID- 25058584 OWN - NLM STAT- MEDLINE DCOM- 20151113 LR - 20240314 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 9 IP - 7 DP - 2014 TI - The impact of maternal cigarette smoke exposure in a rodent model on renal development in the offspring. PG - e103443 LID - 10.1371/journal.pone.0103443 [doi] LID - e103443 AB - 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. FAU - Al-Odat, Ibrahim AU - Al-Odat I AD - School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia; Renal Medicine, Kolling Institute, St Leonards, NSW, Australia. FAU - Chen, Hui AU - Chen H AD - School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia. FAU - Chan, Yik Lung AU - Chan YL AD - School of Medical and Molecular Biosciences, The University of Technology Sydney, Ultimo, NSW, Australia. FAU - Amgad, Sawiris AU - Amgad S AD - Renal Medicine, Kolling Institute, St Leonards, NSW, Australia. FAU - Wong, Muh Geot AU - Wong MG AD - Renal Medicine, Kolling Institute, St Leonards, NSW, Australia. FAU - Gill, Anthony AU - Gill A AD - Anatomical pathology, Northern Clinical School, St Leonards, NSW, Australia. FAU - Pollock, Carol AU - Pollock C AD - Renal Medicine, Kolling Institute, St Leonards, NSW, Australia. FAU - Saad, Sonia AU - Saad S AD - Renal Medicine, Kolling Institute, St Leonards, NSW, Australia. LA - eng PT - Journal Article DEP - 20140724 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Albumins) RN - 0 (Chemokine CCL2) RN - AYI8EX34EU (Creatinine) SB - IM MH - Albumins/metabolism MH - Animals MH - Chemokine CCL2/genetics/metabolism MH - Creatinine/metabolism MH - Female MH - Gene Expression Regulation, Developmental/*drug effects MH - Male MH - Maternal Exposure/*adverse effects MH - Mice MH - Mice, Inbred BALB C MH - Models, Animal MH - Nephrons/metabolism/*pathology/physiopathology MH - Pregnancy MH - Prenatal Exposure Delayed Effects/chemically induced/*metabolism/pathology MH - Smoking/*adverse effects PMC - PMC4110029 COIS- Competing Interests: There is no financial conflict of interest for all the authors. EDAT- 2014/07/25 06:00 MHDA- 2015/11/14 06:00 PMCR- 2014/07/24 CRDT- 2014/07/25 06:00 PHST- 2014/03/02 00:00 [received] PHST- 2014/07/01 00:00 [accepted] PHST- 2014/07/25 06:00 [entrez] PHST- 2014/07/25 06:00 [pubmed] PHST- 2015/11/14 06:00 [medline] PHST- 2014/07/24 00:00 [pmc-release] AID - PONE-D-14-09675 [pii] AID - 10.1371/journal.pone.0103443 [doi] PST - epublish SO - PLoS One. 2014 Jul 24;9(7):e103443. doi: 10.1371/journal.pone.0103443. eCollection 2014.