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

A male offspring sub-fertility phenotype induced by a mouse model of paternal obesity is exacerbated by the same obesogenic diet (#149)

Tod Fullston 1 , Nicole McPherson , Wan Xian Kang , Lauren Sandeman 1 , Michelle Lane 1 2
  1. Discipline of Obstetrics & Gynaecology, School of Paediatrics and Reproductive Health & The Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
  2. Repromed, Adelaide, SA, Australia

The prevalence of obesity and related comorbidities are continually increasing globally. We have previously demonstrated that paternal high fat diet (HFD) exposure programs subsequent generations of rodents for metabolic and reproductive dysfunction.

Our previous reports have documented the subfertility phenotype of male offspring sired by HFD fed fathers, despite being fed a control diet (CD). This subfertility phenotype manifests as reduced sperm motility, reduced oocyte binding and increased intracellular reactive oxygen species (ROS) in sperm.

We used our C57Bl/6 mouse model of HFD induced paternal obesity to sire male offspring and subsequently expose them to the same obesogenic HFD, to model an environment that is frequently shared between an obese father and his children.  This model exposed both fathers and male offspring to a HFD that mimics a ‘western-style’ fast food diet from 5 weeks of age for 12-17 weeks. We then investigated what impact a HFD challenge to male offspring (sired by a HFD father) had on their pre-existing subfertility phenotype.

Regardless of their father’s diet, HFD consumption increased total body weight and adiposity of male offspring. Additionally, offspring sired by HFD male had cumulative gains in total body weight and adiposity compared to their CD sired counterparts. Whereby HFD fed offspring sired by a HFD father had the greatest total body weight and greatest adiposity.

Sperm motility and oocyte binding were similarly reduced by either a father’s or a son’s HFD consumption, concomitant with cumulative increases in sperm intracellular ROS concentrations. The least fertile group were the male offspring sired by a HFD father who consumed a HFD themselves. This indicates that the reproductive impairment of male offspring sired by HFD fathers is exacerbated by their consumption of the same obesogenic diet. This predicts sombre reproductive outcomes in light of the current intergenerational global obesity epidemic.