Effects of paternal alcoholism on the psycho-behavioural outcomes of the offspring: a systematic review and meta-analysis

Mahesh, Pasyodun Koralage Buddhika; Leung, Janni; Senananayake, Sameera; Kumarapeli, Vindya; Ferdinando, Ruwan; Jayawickrama, Withanage iresha Udayanagani; Lakmini, W. D.; Perera, Chiara; Thasleem, Shanaz; McLaughlin, Deirdre

doi:10.4038/jccpsl.v27i3.8398

Cited by 1 publication

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References 60 publications

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“…Studies in humans found that paternal AUD was associated with increased rates of anxiety and depression symptoms particularly in the male offspring (Mahesh et al, 2021). While our lab found no differences in anxiety like behaviours in the ADT, D1 males showed a reduction in rearing behaviours which is taken as an indication of reduced anticipatory behaviour, a symptom of depression.…”

Section: Sex X Ppac Interactions In Depression and Anxiety Behaviourscontrasting

confidence: 55%

“…Unfortunately, most of these studies looked at the maternal effects on offspring behaviour and it has been noted that preference in intergenerational studies is often given to conduct disorders (Easey & Sharp, 2021). Nevertheless, one systematic review of human studies found significant links between fathers with AUD and depressive symptoms in their offspring (particularly males) later in life (Mahesh et al, 2021). Rodent studies parse this association further with mice of ethanol sired rats showing increased anxiety and an increase in depressive like behaviours, particularly in females (Kim, P. et al, 2014;Liang et al, 2014).…”

Section: Depression and Anxietymentioning

confidence: 99%

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Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

Hussain

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Alcohol is the most harmful drug of abuse, making alcoholism a major economic and public health crisis. Unsurprisingly, this has led to the majority of neurobiological research on alcohol focussing on its direct effects on an individual. This includes those affected by foetal alcohol spectrum disorders (FASDs). However, research has shown that heavy paternal drinking predicts earlier and heavier adolescent drinking in the offspring, accompanied with other behavioural and molecular changes. While alcohol use disorder (AUD) is highly heritable, research on genetic variants alone does not sufficiently account for its risk and the FASDs like symptoms seen in the offspring of alcoholic fathers. Recently, there has been an increase in appreciation of the importance of epigenetic mechanisms of inheritance, which transfer changes due to parental experiences through the germline. This thesis aimed to assess both the inter and transgenerational impacts of preconceptual paternal alcohol consumption (PPAC) 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.PPAC 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 of PPAC were seen with female offspring having a reduced preference to ethanol in both the F1 and F2, while tolerance to ethanol in motor coordination was again 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.Analysis of liver mitochondrial DNA copy number (mtDNA-CN) found that drinking F0 fathers had reduced mtDNA-CN at the end of the ethanol intake paradigm and 12 weeks post-drinking relative to controls. The livers of F1 showed lower mtDNA-CN in the offspring of ethanol sired rats compared to offspring of non-drinkers after undergoing ethanol consumption, suggesting differences in liver metabolism. Finally, livers of F0 drinkers had reduced expression of Peroxisome proliferator-activated receptor γ coactivator 1α (Pgc1a), relating to mitochondrial biogenesis, and methyl-CpG-binding protein 2 (Mecp2), indicating putative changes in methylation signalling, together suggesting epigenetic inheritance of changes due to xenotoxic stress.The findings show PPAC induces developmental delays, causes transgenerational changes in drinking behaviour, ethanol sensitivity and liver mitochondrial function in a sexually dimorphic manner. These changes may be protective to the female offspring of PPAC to modify their ethanol intake. The alterations in F1 liver mtDNA-CN demonstrate potential far-reaching consequences for the metabolism of xenotoxic substances extending beyond ethanol and provides evidence to support behavioural and epigenetic changes across generations due to PPAC.

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Section: Sex X Ppac Interactions In Depression and Anxiety Behaviourscontrasting

confidence: 55%

Section: Depression and Anxietymentioning

confidence: 99%

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

Hussain

View full text Add to dashboard Cite

show abstract

Effects of paternal alcoholism on the psycho-behavioural outcomes of the offspring: a systematic review and meta-analysis

Cited by 1 publication

References 60 publications

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

Transgenerational Hangovers: A Rat Model for Behavioural and Epigenetic Changes Across Generations due to Paternal Preconceptual Alcohol Consumption

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