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

Paternal transmission of metabolic and cardio-renal dysfunction to offspring born to a growth restricted father (#184)

Mary E Wlodek 1 , Tina N Hosseini 1 , Andrew J Jefferies 1 , Yasmin Asif 2 , Paul Soeding 3 , Karen M Moritz 4
  1. Physiology, University of Melbourne, Parkville, VIC, Australia
  2. Centre for Physical Activity and Nutrition Research, School of Exercise and Nutrition Sciences, Deakin University, Burwood, VIC, Australia
  3. Pharmacology, University of Melbourne, Parkville, VIC, Australia
  4. School of Biomedical Sciences, University of Queensland, St Lucia, QLD, Australia

Being born small increases cardio-renal and metabolic disease risk which are not limited to the first generation (F1) but can be transmitted to the next generation (F2) with limited evidence of paternal line transmission. We characterised cardio-renal and metabolic phenotype of F2 offspring born to normally grown and growth restricted (F1) fathers.

Late gestation rat uteroplacental insufficiency was induced (Restricted) or sham (Control) surgery in F0. F1 males were mated with normal females. F2 offspring body weight was not different at birth. Males, but not females, from Restricted fathers had altered glucose control following an IPGTT at 6 months (higher area under glucose curve; reduced first phase insulin secretion). Creatinine clearance was reduced in Restricted males at 6 months. Restricted F2 males had evidence of increased left ventricular wall thickness (+10%), left ventricular hypertrophy (+10% at post mortem) and concentric remodelling (echocardiography) which emerged at 16 months in the absence of altered heart contractility. Tail cuff blood pressure was not different at 6, 9, 12 and 16 months of age. Systolic and mean arterial blood pressure (telemetry) at 16 months, was increased during both 12h light and 12h dark periods and was elevated in response to restraint stress (at 30 minutes) and sustained into the early recovery period.

F2 offspring, born to F1 growth restricted fathers are not programmed to be born of low birth weight but developed altered glucose control in the absence of obesity. Male offspring developed concentric remodelling, left ventricular hypertrophy and high blood pressure at 16 months. Our findings provide novel evidence of transmission of metabolic effects as well as signs of an adverse cardiovascular phenotype with aging in F2 males via the paternal line in an uteroplacental insufficiency model of growth restriction. Females were protected from these programmed disease risks.