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

Influence of uteroplacental insufficiency on blood pressure and arterial wall stiffness in first and second generation aged male rats. (#188)

Jean N Cheong 1 , Maria Jelinic 2 , Andrew J Jefferies 1 , Antonio Pre 1 , Laura J Parry 2 , Karen M Moritz 3 , Mary E Wlodek 1
  1. Department of Physiology, The University of Melbourne, Parkville, Victoria, Australia
  2. Department of Zoology, The University of Melbourne, Parkville, Victoria, Australia
  3. School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland, Australia

Intrauterine growth restriction increases the risk of cardiovascular disease, with males exhibiting a more severe phenotype than females. These disease risks in the first, directly exposed generation (F1) may be transmitted to the next generation (F2). Maternal stress during pregnancy impacts fetal development, however, its effect on mothers who were born small is not understood. We characterised the cardiovascular phenotype of F1 growth restricted males and F2 males born to growth restricted F1 mothers. We also determined whether F1 maternal stress during late pregnancy exacerbates the F2 phenotype. 

Late gestation uteroplacental insufficiency was induced on E18 of pregnancy by bilateral uterine vessel ligation (Restricted) or sham (Control) surgery in F0 females to generate F1 males. F1 female offspring (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. Body weights were measured from birth and tail cuff blood pressure measured to 16 months (mo). At 14-16mo arterial stiffness of small renal and mesenteric arteries was assessed using pressure myography.

Restricted F1 males had reduced birth weight (-18%) with no differences in blood pressure. F2 males born to Control or Restricted F1 mothers exposed to maternal stress had reduced birth weight (-4-6%). Restricted Unstressed males had higher blood pressure (6,12mo) compared to Control Unstressed. Control Stressed male offspring had elevated blood pressure (6,9,12mo) compared to Control Unstressed. However, arterial wall stiffness did not differ in both F1 and F2 males.

F1 growth restricted males had normal blood pressure and arterial wall stiffness although they were born of a lower birth weight. F2 males were born small if their mothers experienced maternal stress. The second hit of maternal stress programmed hypertension without influencing arterial wall stiffness.