ESA-SRB-AOTA 2019

Paternal exposure to a toxicant across multiple generations is detrimental to the reproductive health of male progeny (#12)

Caitlin G Chambers 1 2 3 , Brett Nixon 1 2 , Shaun D Roman 1 2 3
  1. Discipline of Biology, School of Environmental and Life Sciences, University of Newcastle, Callaghan, New South Wales, Australia
  2. The Priority Research Centre for Reproductive Biology, University of Newcastle, Callaghan, New South Wales, Australia
  3. The Priority Research Centre for Drug Development, University of Newcastle, Callaghan, New South Wales, Australia

Humans are chronically exposed to acrylamide in carbohydrate-rich foods cooked above 120°C. We previously demonstrated that chronic administration of acrylamide to male mice, at a human-relevant dose (1 µg/mL drinking water for 6 months (M)) increased DNA damage in spermatozoa [1]. Thus, there is a concern for the increased susceptibility of offspring to acrylamide-induced DNA damage. To explore this possibility, we utilised a shorter exposure regimen (3M at 1 µg/mL acrylamide) and extended the study to the F2 generation. In addition, we conducted exposure studies on both the F1 and F2 generations. We demonstrated that the shorter exposure regimen increased DNA fragmentation in spermatozoa of acrylamide-exposed F0 males (128% of control), replicated in the F1 generation, where DNA fragmentation was elevated in spermatozoa from the exposed progeny of unexposed fathers (154% of control). We determined the unexposed F1 progeny of F0 exposed males had increased DNA fragmentation in their spermatozoa (136% of control), whilst their exposed F1 littermates had DNA fragmentation equal to the unexposed progeny of F0 controls. Following exposure to the F2 generation, we established grand-paternal exposure elevated DNA fragmentation in spermatozoa of F2 progeny (115-135% of control) irrespective of exposure to the F1 or F2. Furthermore, we demonstrated significant correlations between DNA damage in the fathers (F0 or F1) and that of their male progeny (F1 or F2). This study also revealed that grand-paternal acrylamide exposure significantly affected the male reproductive tract, with reduced testis to body weight ratio of F2 progeny, regardless of F1 or F2 exposure.

This study provided the first evidence that acrylamide results in transgenerational damage extending to the F2 generation. This study also demonstrates that paternal and grand-paternal acrylamide exposure has a detrimental effect on male offspring and their genetic potential with, or without, further exposure to acrylamide

 

  1. Katen AL, Chambers CG, Nixon B, Roman SD. Chronic acrylamide exposure in male mice results in elevated DNA damage in the germline and heritable induction of CYP2E1 in the testes. Biol Reprod. 2016;95(4):Article 86, 1-15.