Poster Presentation The Annual Scientific Meeting of the Endocrine Society of Australia and the Society for Reproductive Biology 2014

Influence of maternal stress during pregnancy in female rats born small on second generation male metabolic and pancreatic outcomes. (#211)

Jean N Cheong 1 , Andrew J Jefferies 1 , Kristina Anevska 1 , Karen M Moritz 2 , Mary E Wlodek 1
  1. Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
  2. School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland, Australia

Intrauterine growth restriction increases the risk of adult metabolic diseases, with males exhibiting more severe phenotypes than females. These disease risks are not limited to the first, directly exposed generation (F1) but may be transmitted to the next generation (F2). Stress during pregnancy adversely impacts fetal development, however, its effect on mothers born small is not understood. We characterised the metabolic phenotype of F2 males born to growth restricted F1 mothers and determined if maternal stress during late pregnancy exacerbated the phenotype.

Late gestation uteroplacental insufficiency was induced on E18 by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery in F0 females. F1 females (Control, Restricted) were mated with a male rat and allocated to Unstressed or Stressed groups. Physiological stressors (24h metabolic cage, tail cuff blood pressure, glucose tolerance test) were introduced during late pregnancy in the Stressed group. F2 body weights were measured, metabolic function characterised (fasting glucose tolerance test and insulin challenge) and pancreatic β-cell and islet mass quantified.

F2 males from mothers exposed to maternal stress had reduced birth weight (-4-6%). At 6 months (mo), Control and Restricted F2 males from Stressed mothers developed impaired glucose tolerance compared with offspring from Unstressed mothers which normalised by 12mo. Insulin sensitivity and secretion were not altered at both ages. Compared to Control counterparts, Unstressed Restricted males had decreased β-cell and islet mass (-17-21%) at 6mo with these deficits exacerbated in Stressed Restricted males (-40-42%). Pancreatic deficits restored to normal by 12mo.

Mothers exposed to modest stress during late pregnancy, independent of maternal birth weight, reduced F2 birth weight and programmed metabolic dysfunction. Maternal low birth weight programmed pancreatic deficits in F2 males that were subsequently normalised, demonstrating β-cell plasticity. These offspring may be predisposed to differential responses when challenged with second-hits including unhealthy diets and sedentary lifestyles.