Preconceptual paternal ethanol drinking induces sexually dimorphic behavioural changes across 2 generations

Hussain, Sahir and Day, Darren and Ellenbroek, Bart A (2025) Preconceptual paternal ethanol drinking induces sexually dimorphic behavioural changes across 2 generations. Psychopharmacology. ISSN 0033-3158

Abstract

This study aimed to assess both the inter and transgenerational impacts of preconceptual paternal ethanol Exposure (PPEE) using a rat model. Sprague Dawley male rats (F0) underwent chronic voluntary ethanol intake and at the end of the drinking paradigm were kept for one spermatogenesis cycle before being mated with ethanol naïve females. The litters and matched controls were behaviourally assessed, and a cohort of F1 males mated to observe a F2 generation. PPEE caused behavioural changes in both the F1 and F2 generations, including altering litter sizes and delaying development. The F1 also show a reduction in sensitivity to the motor impairing effects of ethanol compared to controls. Sexually dimorphic effects were seen with female offspring having a reduced preference to ethanol in both the F1 and F2, while tolerance to ethanol induced motor coordination was seen in the F2 females but not F2 males. Likewise, F1 males presented reductions in locomotor activity but these effects did not persist in the F2. The findings show PPEE induces transgenerational changes in development, drinking behaviour and ethanol sensitivity in a sexually dimorphic manner. These changes may be protective to the female offspring of PPEE to modify their ethanol intake. The alterations demonstrate potential far-reaching consequences for the metabolism of xenotoxic substances extending beyond ethanol and provides evidence to support developmental and behavioural changes across generations due to paternal alcohol consumption.