The Joint Annual Scientific Meetings of the Endocrine Society of Australia and the Society for Reproductive Biology 2018

Transgenerational impacts of paternal stress on offspring behavioural phenotypes and stress-response (#79)

Annabel K Short 1 , Katie A Fennell 2 , Shlomo Yeshurun 2 , Arina Rawat 2 3 , Vicky Batchelor 2 3 , Anthony Hannan 2 3 , Terence Y Pang 2 3
  1. Department of Pediatrics, UC Irvine Health, Irvine, CA, United States of America
  2. Florey Institute of Neuroscience and Mental Health, UNIVERSITY OF MELBOURNE, VIC, Australia
  3. Anatomy & Neuroscience, University of Melbourne, Parkville, VIC, AUSTRALIA

Parental preconception exposures to non-genetic and environmental challenges including stress, imbalanced nutritional intake, and drugs of abuse, can impact offspring behaviour, health and risk for disease. There is growing evidence of these transgenerational influences evidenced from retrospective human studies and multiple animal models. While the maternal influence and the mode of transmission is well-studied, the extent of paternal inheritance remains poorly understood. Our lab has developed a mouse model of physical stress in which male breeders are provided corticosterone supplementation in drinking water (Short et. al., 2016). The resulting adult male F1 offspring display heightened levels of anxiety, with abnormal anxiety behaviours also observed in F2 generation. Interestingly, only juvenile female F1 offspring display abnormal patterns of fear extinction. More recent work has also revealed alterations in the drug-response and stress-responsivity of the F1 generation (Rawat et. al., in press). To begin to elucidate the origin of these shifts in offspring phenotypes, small RNA sequencing analysis of male breeders revealed significant changes in the expression levels of sperm-borne microRNAs. Consistent with transmission via the male germ line, expression of the paternally-imprinted gene igf2 was down-regulated in the hippocampus of F1 and F2 male offspring despite being unaltered in F0 breeders. Finally, I will speculate on the potential mechanisms linking stress exposure to the changed molecular profile of sperm.