Fetal growth restriction followed by early catch-up growth impairs pancreatic islet morphology in male rats.

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    • Source:
      Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
    • Publication Information:
      Original Publication: London : Nature Publishing Group, copyright 2011-
    • Subject Terms:
      Glucose Intolerance*/pathology ; Diabetes Mellitus, Type 2*/complications ; Islets of Langerhans*/metabolism; Pregnancy ; Humans ; Female ; Animals ; Rats ; Male ; Fetal Growth Retardation/metabolism ; Animals, Newborn ; Fibrosis
    • Abstract:
      Fetal growth restriction (FGR), followed by postnatal early catch-up growth, is associated with an increased risk of metabolic dysfunction, including type 2 diabetes in humans. This study aims to determine the effects of FGR and early catch-up growth after birth on the pathogenesis of type 2 diabetes, with particular attention to glucose tolerance, pancreatic islet morphology, and fibrosis, and to elucidate its mechanism using proteomics analysis. The FGR rat model was made by inducing mild intrauterine hypoperfusion using ameroid constrictors (ACs). On day 17 of pregnancy, ACs were affixed to the uterine and ovarian arteries bilaterally, causing a 20.9% reduction in birth weight compared to sham pups. On postnatal day 4 (P4), the pups were assigned to either the good nutrition (GN) groups with 5 pups per dam to ensure postnatal catch-up growth or poor nutrition groups with 15 pups per dam to maintain lower body weight. After weaning, all pups were fed regular chow food ad libitum (P21). Rats in both FGR groups developed glucose intolerance; however, male rats in the FGR good nutrition (FGR-GN) group also developed hypertriglyceridemia and dysmorphic pancreatic islets with fibrosis. A comprehensive and functional analysis of proteins expressed in the pancreas showed that FGR, followed by early catch-up growth, severely aggravated cell adhesion-related protein expression in male offspring. Thus, FGR and early catch-up growth caused pancreatic islet morphological abnormalities and fibrosis associated with the disturbance of cell adhesion-related protein expressions. These changes likely induce glucose intolerance and dyslipidemia in male rats.
      (© 2023. The Author(s).)
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    • Publication Date:
      Date Created: 20230215 Date Completed: 20230217 Latest Revision: 20230329
    • Publication Date:
      20240628
    • Accession Number:
      PMC9932152
    • Accession Number:
      10.1038/s41598-023-28584-2
    • Accession Number:
      36792668