{"title":"父亲在受孕前饮用乙醇会导致两代人的两性二态行为改变。","authors":"Sahir Hussain, Darren Day, Bart A Ellenbroek","doi":"10.1007/s00213-025-06807-w","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Preconceptual paternal ethanol drinking induces sexually dimorphic behavioural changes across 2 generations.\",\"authors\":\"Sahir Hussain, Darren Day, Bart A Ellenbroek\",\"doi\":\"10.1007/s00213-025-06807-w\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>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.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-05-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Psychopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00213-025-06807-w\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06807-w","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
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.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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