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. and Cullen-McEwen, Lusie A. 2016, Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring, Diabetes/metabolism research and reviews, vol. 32, no. 8, pp. 816-826, doi: 10.1002/dmrr.2805.

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Title Maternal glucose intolerance reduces offspring nephron endowment and increases glomerular volume in adult offspring
Author(s) Hokke, Stacey
Arias, Nicole
Armitage, James A.ORCID iD for Armitage, James A.
Puelles, Victor G.
Fong, Karen
Geraci, Stefania
Gretz, Norbert
Bertram, John F.
Cullen-McEwen, Lusie A.
Journal name Diabetes/metabolism research and reviews
Volume number 32
Issue number 8
Start page 816
End page 826
Total pages 11
Publisher Wiley
Place of publication Chichester, Eng.
Publication date 2016-11
ISSN 1520-7560
Keyword(s) kidney development
renal function
maternal diabetes
impaired glucose tolerance
developmental programming
nephron number
Summary 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.
Language eng
DOI 10.1002/dmrr.2805
Field of Research 1103 Clinical Sciences
Socio Economic Objective 920104 Diabetes
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2016, John Wiley & Sons
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Document type: Journal Article
Collections: Faculty of Health
School of Medicine
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