Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring

Stacey Hokke, Nicole Arias, James A. Armitage, Victor G. Puelles, Karen Fong, Stefania Geraci, Norbert Gretz, John F. Bertram, Luise A. Cullen-McEwen

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.
Original languageEnglish
Pages (from-to)816-826
Number of pages11
JournalDiabetes/Metabolism Research and Reviews
Volume32
Issue number8
DOIs
Publication statusPublished - Nov 2016

Keywords

  • kidney development
  • renal function
  • maternal diabetes
  • impaired glucose tolerance
  • developmental programming
  • nephron number

Cite this

@article{f3471eaaf6c44ece84b1a5280b98896d,
title = "Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring",
abstract = "Background: 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. Methods: 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. Results: 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. Conclusions: 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.",
keywords = "kidney development, renal function, maternal diabetes, impaired glucose tolerance, developmental programming, nephron number",
author = "Stacey Hokke and Nicole Arias and Armitage, {James A.} and Puelles, {Victor G.} and Karen Fong and Stefania Geraci and Norbert Gretz and Bertram, {John F.} and Cullen-McEwen, {Luise A.}",
year = "2016",
month = "11",
doi = "10.1002/dmrr.2805",
language = "English",
volume = "32",
pages = "816--826",
journal = "Diabetes/Metabolism Research and Reviews",
issn = "1520-7560",
publisher = "John Wiley & Sons",
number = "8",

}

Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring. / Hokke, Stacey; Arias, Nicole; Armitage, James A.; Puelles, Victor G.; Fong, Karen; Geraci, Stefania; Gretz, Norbert; Bertram, John F.; Cullen-McEwen, Luise A.

In: Diabetes/Metabolism Research and Reviews, Vol. 32, No. 8, 11.2016, p. 816-826.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring

AU - Hokke, Stacey

AU - Arias, Nicole

AU - Armitage, James A.

AU - Puelles, Victor G.

AU - Fong, Karen

AU - Geraci, Stefania

AU - Gretz, Norbert

AU - Bertram, John F.

AU - Cullen-McEwen, Luise A.

PY - 2016/11

Y1 - 2016/11

N2 - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

AB - Background: 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. Methods: 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. Results: 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. Conclusions: 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.

KW - kidney development

KW - renal function

KW - maternal diabetes

KW - impaired glucose tolerance

KW - developmental programming

KW - nephron number

UR - http://www.ncbi.nlm.nih.gov/pubmed/27037899

U2 - 10.1002/dmrr.2805

DO - 10.1002/dmrr.2805

M3 - Article

VL - 32

SP - 816

EP - 826

JO - Diabetes/Metabolism Research and Reviews

JF - Diabetes/Metabolism Research and Reviews

SN - 1520-7560

IS - 8

ER -