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Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats

Jensen, Vivi F.H. LU ; Mølck, Anne Marie ; Bøgh, Ingrid B. ; Nowak, Jette ; Viuff, Birgitte M. ; Rasmussen, Charlotte L.M. ; Pedersen, Louise ; Fels, Johannes J. ; Madsen, Suzi H. and McGuigan, Fiona E. LU orcid , et al. (2020) In Scientific Reports 10(1).
Abstract

Maternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and... (More)

Maternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and decreased cellular density; expression of pro-angiogenic factors, HIF-1α and VEGF-A increased in surrounding areas. Disproportionately decreased growth plate zone volumes and lower expression of the structural protein MATN-3 were seen, while bone ossification parameters were normal. Ending maternal/foetal hypoglycaemia on GD17 reduced incidence and severity of histopathologic changes and with normal growth plate volume. Compromised foetal skeletal development following maternal hypoglycaemia throughout gestation is hypothesised to result from corticosterone-induced hypoxia in growth plates, where hypoxia disrupts chondrocyte maturation and growth plate structure and volume, decreasing long bone growth. Maternal/foetal hypoglycaemia lasting only until GD17 attenuated these changes, suggesting a pivotal role of glucose in growth plate development.

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publishing date
type
Contribution to journal
publication status
published
subject
in
Scientific Reports
volume
10
issue
1
article number
5609
publisher
Nature Publishing Group
external identifiers
  • scopus:85082535927
  • pmid:32221393
ISSN
2045-2322
DOI
10.1038/s41598-020-62554-2
language
English
LU publication?
yes
id
b364a717-c0ba-43e7-8684-e6b512289a45
date added to LUP
2020-04-15 16:08:33
date last changed
2024-04-03 06:06:18
@article{b364a717-c0ba-43e7-8684-e6b512289a45,
  abstract     = {{<p>Maternal hypoglycaemia throughout gestation until gestation day (GD)20 delays foetal growth and skeletal development. While partially prevented by return to normoglycaemia after completed organogenesis (GD17), underlying mechanisms are not fully understood. Here, we investigated the pathogenesis of these changes and significance of maternal hypoglycaemia extending beyond organogenesis in non-diabetic rats. Pregnant rats received insulin-infusion until GD20 or GD17, with sacrifice on GD20. Hypoglycaemia throughout gestation increased maternal corticosterone levels, which correlated with foetal levels. Growth plates displayed central histopathologic changes comprising disrupted cellular organisation, hypertrophic chondrocytes, and decreased cellular density; expression of pro-angiogenic factors, HIF-1α and VEGF-A increased in surrounding areas. Disproportionately decreased growth plate zone volumes and lower expression of the structural protein MATN-3 were seen, while bone ossification parameters were normal. Ending maternal/foetal hypoglycaemia on GD17 reduced incidence and severity of histopathologic changes and with normal growth plate volume. Compromised foetal skeletal development following maternal hypoglycaemia throughout gestation is hypothesised to result from corticosterone-induced hypoxia in growth plates, where hypoxia disrupts chondrocyte maturation and growth plate structure and volume, decreasing long bone growth. Maternal/foetal hypoglycaemia lasting only until GD17 attenuated these changes, suggesting a pivotal role of glucose in growth plate development.</p>}},
  author       = {{Jensen, Vivi F.H. and Mølck, Anne Marie and Bøgh, Ingrid B. and Nowak, Jette and Viuff, Birgitte M. and Rasmussen, Charlotte L.M. and Pedersen, Louise and Fels, Johannes J. and Madsen, Suzi H. and McGuigan, Fiona E. and Tveden-Nyborg, Pernille and Lykkesfeldt, Jens and Akesson, Kristina E.}},
  issn         = {{2045-2322}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Scientific Reports}},
  title        = {{Inner histopathologic changes and disproportionate zone volumes in foetal growth plates following gestational hypoglycaemia in rats}},
  url          = {{http://dx.doi.org/10.1038/s41598-020-62554-2}},
  doi          = {{10.1038/s41598-020-62554-2}},
  volume       = {{10}},
  year         = {{2020}},
}