title: Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring.
abstract: Animal studies report a nephron deficit in offspring exposed to maternal diabetes, yet are limited to models of severe hyperglycaemia which do not reflect the typical clinical condition and which are associated with foetal growth restriction that may confound nephron endowment. We aimed to assess renal morphology and function in offspring of leptin receptor deficient mice (Leprdb/+) and hypothesized that exposure to impaired maternal glucose tolerance (IGT) would be detrimental to the developing kidney.
  
  
  
  Nephron endowment was assessed in offspring of C57BKS/J Leprdb/+ and +/+ mice at embryonic day (E)18 and postnatal day (PN)21 using design-based stereology. Transcutaneous measurement of renal function and total glomerular volume were assessed in 6-month-old offspring. Only +/+ offspring of Leprdb/+ dams were analysed.
  
  
  
  Compared with +/+ dams, Leprdb/+ dams had a 20% and 35% decrease in glucose tolerance prior to pregnancy and at E17.5 respectively. Offspring of IGT Leprdb/+ dams had approximately 15% fewer nephrons at E18.5 and PN21 than offspring of +/+ dams. There was no difference in offspring bodyweight. Despite normal renal function, total glomerular volume was 13% greater in 6-month-old offspring of IGT Leprdb/+ dams than in +/+ offspring.
  
  
  
  IGT throughout gestation resulted in a nephron deficit that was established early in renal development. Maternal IGT was associated with glomerular hypertrophy in adult offspring, likely a compensatory response to maintain normal renal function. Given the increasing prevalence of IGT, monitoring glucose from early in gestation may be important to prevent altered kidney morphology. Copyright © 2016 John Wiley & Sons, Ltd.
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Stacey
authors.initials: S
authors.lastname: Hokke
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Nicole
authors.initials: N
authors.lastname: Arias
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.|School of Medicine (Optometry), Deakin University, Waurn Ponds, VIC, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Armitage
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Victor G
authors.initials: VG
authors.lastname: Puelles
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: Karen
authors.initials: K
authors.lastname: Fong
authors.affiliation: Medical Research Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Stefania
authors.initials: S
authors.lastname: Geraci
authors.affiliation: Medical Research Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia.
authors.forename: John F
authors.initials: JF
authors.lastname: Bertram
authors.affiliation: Development and Stem Cells Program, Monash Biomedicine Discovery Institute, and Department of Anatomy and Developmental Biology, Monash University, Clayton, VIC, Australia. luise.cullen-mcewen@monash.edu.
authors.forename: Luise A
authors.initials: LA
authors.lastname: Cullen-McEwen
mesh_terms: D000818:Animals; D016640:Diabetes, Gestational / Q000503:physiopathology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005260:Female; D005317:Fetal Growth Retardation / Q000209:etiology* / Q000473:pathology; D018149:Glucose Intolerance / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000254:growth & development / Q000473:pathology*; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009399:Nephrons / Q000254:growth & development / Q000473:pathology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D054411:Receptors, Leptin / Q000502:physiology*; D015430:Weight Gain
chemical_list: D054411:Receptors, Leptin
keywords: developmental programming; impaired glucose tolerance; kidney development; maternal diabetes; nephron number; renal function