Growth factors in the fetus and pre-adolescent offspring of hyperglycemic rats

Diab Vasc Dis Res. 2021 Mar-Apr;18(2):14791641211011025. doi: 10.1177/14791641211011025.

Abstract

Background: Maternal hyperglycemia influences childhood metabolic syndrome, including obesity and hyperglycemia. We tested the hypothesis that the maternal hyperglycemia influences growth factors in the fetal and pre-adolescent offspring.

Methods: Hyperglycemia was induced in pregnant rats on embryonic day (E)16 using streptozocin followed by implantation with insulin or placebo pellets at embryonic day 18 (E18). Fetuses at E20 and pre-adolescent pups at postnatal day 14 (P14) were studied: (1) normal untreated controls (CTL) at E20; (2) hyperglycemic placebo-treated (HPT) at E20; (3) hyperglycemic insulin-treated (HIT) at E20; (4) CTL at P14; and (5) HIT at P14. Fetal and pre-adolescent growth factors were determined.

Results: Biomarkers of hypoxia were elevated in the HPT group at E20. This group did not survive to term. Maternal insulin improved fetal survival despite lower fetal body weight at E20, however, at normal birth (postnatal day 0 (P0)) and at P14, body weights and blood glucose were higher than CTL. These high levels correlated with aberrant growth factors. Maternal hyperglycemia influenced glucose-6-phosphate dehydrogenase, glucagon, insulin, interleukin-10, and leptin genes.

Conclusions: The impact of maternal hyperglycemia on pre-adolescent glucose and body weight was not a consequence of maternal overnutrition. This suggests an independent link which may affect offspring metabolic health in later life.

Keywords: Fetus; glucose; growth factors; insulin; maternal hyperglycemia.

MeSH terms

  • Age Factors
  • Animals
  • Biomarkers / blood
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism*
  • Diabetes, Gestational / blood*
  • Diabetes, Gestational / drug therapy
  • Disease Models, Animal
  • Female
  • Fetus / metabolism*
  • Gene Expression Regulation
  • Gestational Age
  • Hypoglycemic Agents / pharmacology
  • Insulin / pharmacology
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Biomarkers
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Intercellular Signaling Peptides and Proteins