Oral Presentation ESA-SRB Conference 2015

A paternal high fat diet alters founder sperm microRNA profile and implicates it as part of a candidate epigenetic mechanism underlying paternal programing. (#9)

Tod Fullston , Nicole O McPherson 1 2 , Wan Xian Kang 1 , Lauren Sandeman 1 , Julie A Owens 1 , Michelle Lane 1 3
  1. Discipline of Obstetrics & Gynaecology, School of Paediatrics and Reproductive Health, Robinson Institute, The University of Adelaide, Adelaide, SA, Australia
  2. Freemasons Foundation Centre for Men’s Health, The University of Adelaide, Adelaide, SA, Australia
  3. Monash IVF Group, Melbourne, VIC, Australia

Obesity and related comorbidities are increasingly globally prevalent.  We have previously demonstrated that a paternal high fat diet (HFD) programs two subsequent generations of mice for reproductive and metabolic dysfunction.

We now demonstrate that a paternal HFD concomitantly shifts the mircoRNA profile of sperm.  28 sperm borne microRNAs were initially indicated as being differentially abundant by qPCR array card (n=4 per CD/HFD).  Subsequently 13/28 microRNAs were confirmed as differentially abundant in sperm from three separate cohorts of mice fed a HFD by individual qPCR assays (n=13 CD/14 HFD).  Interestingly 2/13 of these miroRNAs were: (i) upregulated by the HFD; (ii) are presumed sperm specific (not detectable in oocytes, present in zygotes) and (iii) their homologs are amongst the most abundant microRNAs in human sperm.  Experimentally validated, developmentally important mRNA targets (Oct4, Sox2) of one of the sperm specific microRNAs have altered expression in zygotes sired by HFD males.

Preliminary analysis suggests that the same microRNAs might also be dysregualted in sperm of offspring from HFD fed founder males, albeit in an inverse direction and despite being separated by a chasm of developmental time.

HFD fed founder sperm microRNA content appears to be somewhat restored by interventions that target obesity (diet and/or exercise).  This partial restoration of sperm microRNA content occurs with partial restoration of subfertility and metabolic phenotypes in offspring born to HFD fed founders.

Overall this suggests sperm borne microRNAs form part of an epigenetic mechanism, sensitive to the dietary/metabolic state of a male, capable of having molecular consequences in the preimplantation embryo.  This potentially triggers a molecular cascade that impairs embryo development and programs the F1 generation for reproductive and metabolic dysfunction.  Furthermore this information may provide an under-recognised window of opportunity for intervention that holds the potential to improve the health of the future generations.