Glucose intolerance develops prior to increased adiposity and accelerated cessation of estrous cyclicity in female growth-restricted rats

Pediatr Res. 2016 Jun;79(6):962-70. doi: 10.1038/pr.2016.14. Epub 2016 Feb 8.


Background: The incidence of metabolic disease increases in early menopause. Low birth weight influences the age at menopause. Thus, this study tested the hypothesis that intrauterine growth restriction programs early reproductive aging and impaired glucose homeostasis in female rats.

Methods: Estrous cyclicity, body composition, and glucose homeostasis were determined in female control and growth-restricted rats at 6 and 12 mo of age; sex steroids at 12 mo.

Results: Glucose intolerance was present at 6 mo of age prior to cessation of estrous cyclicity and increased adiposity in female growth-restricted rats. However, female growth-restricted rats exhibited persistent estrus and a significant increase in adiposity, fasting glucose, and testosterone at 12 mo of age (P < 0.05). Insulin release in response to a glucose challenge was blunted in conjunction with a reduction in protein expression of pancreatic glucose transporter type 2 and estrogen receptor-α at 12 mo of age in female growth-restricted rats (P < 0.05).

Conclusion: This study demonstrated that slow fetal growth programmed glucose intolerance that developed prior to early estrous acyclicity; yet, fasting glucose levels were elevated in conjunction with increased adiposity, accelerated cessation of estrous cyclicity and a shift toward testosterone excess at 12 mo of age in female growth-restricted rats.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity*
  • Animals
  • Body Composition
  • Estrus*
  • Female
  • Fetal Growth Retardation
  • Glucose / metabolism
  • Glucose Intolerance*
  • Glucose Tolerance Test
  • Homeostasis
  • Menopause
  • Organ Size
  • Rats
  • Testosterone / metabolism
  • Time Factors
  • Uterus / pathology


  • Testosterone
  • Glucose