Maternal background alters the penetrance of growth phenotypes and sex‐specific placental adaptation of offspring sired by alcohol‐exposed males

The FASEB Journal, Journal Year: 2021, Volume and Issue: 35(12)

Published: Nov. 8, 2021

Epigenetic mechanisms of paternal inheritance are an emerging area interest in our efforts to understand fetal alcohol spectrum disorders. In rodent models examining maternal exposures, different genetic backgrounds protect or sensitize offspring alcohol-induced teratogenesis. However, whether background can mitigate sperm-inherited alterations developmental programming and modify the penetrance growth defects induced by preconception exposures remains unaddressed. previous studies pure C57Bl/6J crosses, alcohol-exposed sires exhibited restriction, enlarged placentas, decreased placental efficiency. Here, we find that contrast studies, F1 CD-1 dams do not exhibit with male fetuses developing smaller placentas increased efficiencies. these hybrid offspring, exposure induces sex-specific changes morphology. Specifically, female displayed structural junctional labyrinth zones, along glycogen content. These organization accompanied female-specific expression imprinted genes Cdkn1c H19. Although placentae display overt histology, using RNA-sequencing, identified programmed regulating oxidative phosphorylation, mitochondrial function, Sirtuin signaling. Collectively, data reveal transmits a stressor males females distinct patterns adaptation, modulate effects exposure.

Language: Английский

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Paternal alcohol exposures program intergenerational hormetic effects on offspring fetoplacental growth

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: Aug. 11, 2022

Hormesis refers to graded adaptive responses harmful environmental stimuli where low-level toxicant exposures stimulate tissue growth and responsiveness while, in contrast, higher-level induce toxicity. Although the intergenerational inheritance of programmed hormetic is described plants insects, researchers have yet observe this phenomenon mammals. Using a physiologically relevant mouse model, we demonstrate that chronic preconception paternal alcohol program nonlinear, dose-dependent changes offspring fetoplacental growth. Our studies identify an inverse j-shaped curve with threshold 2.4 g/Kg per day; below threshold, ethanol increases placental growth, while doses exceeding point yield comparative decreases In male offspring, higher labyrinth layer but do not impact fetal hypertrophy induced by associate increased crown-rump length, particularly offspring. Finally, alterations physiology correlate disruptions both mitochondrial-encoded imprinted gene expression. Understanding influence on paternally-inherited epigenetic downstream may help explain enormous variation observed spectrum disorder (FASD) phenotypes incidence.

Language: Английский

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Adaptive Significance of Non-coding RNAs: Insights from Cancer Biology

Molecular Biology and Evolution, Journal Year: 2025, Volume and Issue: 42(1)

Published: Jan. 1, 2025

Abstract The molecular basis of adaptive evolution and cancer progression are both complex processes that share many striking similarities. potential significance environmentally-induced epigenetic changes is currently an area great interest in evolutionary biology. In the field biology intense effort has been focused on contribution stress-induced non-coding RNAs (ncRNAs) activation associated with elevated mutation rates acquisition environmentally traits. Examples this process presented combined more recent findings demonstrating ncRNAs transferable from somatic to germline cells leading cross-generational inheritance acquired fact have implicated transient response various plants animals environmental stress consistent Based these collective observations, a general model as well specific testable hypotheses proposed how ncRNA-mediated responses may facilitate transition long-term biological adaptation evolution.

Language: Английский

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Preconception Paternal Alcohol Consumption Elicits Postnatal Changes in Neural Retinas of the Offspring

Investigative Ophthalmology & Visual Science, Journal Year: 2025, Volume and Issue: 66(2), P. 16 - 16

Published: Feb. 6, 2025

Purpose: This study aims to determine the impact of preconception paternal alcohol consumption (PPAC) on retinal function and morphology in PPAC-offspring. Fetal spectrum disorder (FASD)–related ocular defects caused by maternal exposure has been well investigated, but influence PPAC offspring eyes remains unknown. Methods: Adult C57BL/6J male mice were exposed either 10% ethanol or water (control) for six weeks bred naïve females. Dark-adapted light responses at two, four, months old assessed using electroretinography (ERG) born control males. The thicknesses whole retinas different layers PPAC-offspring analyzed two old. Results: Some had only one developed eye. ERG a- b-wave amplitudes reduced compared controls, with a more pronounced effect significant effects inner function. At old, there was thinning nuclear plexiform thickness similar between both treatment groups. Conclusions: provides pioneering evidence that contributes FASD-related including negative impacts young adult offspring. Thus adverse prior conception their (from childhood early adulthood) should be considered as seriously contribution FASD.

Language: Английский

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From fathers to offspring: epigenetic impacts of diet and lifestyle on fetal development

Epigenetics Insights, Journal Year: 2025, Volume and Issue: 18(1), P. 0 - 0

Published: Jan. 1, 2025

Language: Английский

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Transgenerational Abnormalities Induced by Paternal Preconceptual Alcohol Drinking: Findings from Humans and Animal Models

Current Neuropharmacology, Journal Year: 2021, Volume and Issue: 20(6), P. 1158 - 1173

Published: Nov. 1, 2021

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects gestational alcohol use have been well documented, only recently, role paternal preconceptual (PPAC) prior to copulating has drawn specific epigenetic considerations. Data from human animal models demonstrated that PPAC may affect sperm function, eliciting oxidative stress. In newborns, induce changes behavior, cognitive functions, emotional responses. Furthermore, elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill hearing loss, endocrine, immune alterations, reduced physical growth, placental metabolic alterations. Neurobiological studies on also disclosed brain function structure by disrupting growth factors pathways. particular, as shown model studies, alters nerve factor (NGF) brainderived neurotrophic (BDNF) synthesis release. This review shows crucial topic lifelong disabilities induced and/or drinking quite challenging at individual, societal, familial levels. Since nontoxic behavior before (for both men women), pregnancy, cannot be established, suggestion for couples planning pregnancies completely avoid alcoholic beverages.

Language: Английский

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Paternal Preconception Every-Other-Day Ethanol Drinking Alters Behavior and Ethanol Consumption in Offspring

Brain Sciences, Journal Year: 2019, Volume and Issue: 9(3), P. 56 - 56

Published: March 6, 2019

Alcohol use disorder is a devastating disease with complex etiology. Recent preclinical studies have revealed that paternal preconception chronic intermittent ethanol (EtOH) exposure via vaporized EtOH altered drinking behaviors and sensitivity to selectively in male offspring. In the current study, we used voluntary oral route of exposure, i.e., every-other-day two-bottle choice drinking, tested offspring for behavioral alterations. Fifteen sires 10 control were mated naïve females produce EtOH-sired control-sired These using elevated plus maze, open field, dark, unlimited access assays. We found resulted reduced consumption dark assay compared No differences detected either sex maze Open field analysis changes basal behavior EtOH-induced specific. concluded has persistent effects impact next generation. This study adds growing appreciation one’s response are impacted by prior

Language: Английский

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Programmed increases in LXRα induced by paternal alcohol use enhance offspring metabolic adaptation to high-fat diet induced obesity

Molecular Metabolism, Journal Year: 2019, Volume and Issue: 30, P. 161 - 172

Published: Oct. 3, 2019

Paternally inherited alterations in epigenetic programming are emerging as relevant factors numerous disease states, including the growth and metabolic defects observed fetal alcohol spectrum disorders. In rodents, chronic paternal use induces restriction, well sex-specific insulin signaling lipid homeostasis offspring. Based on previous studies, we hypothesized that irregularities consequence of paternally liver x receptor (LXR) activity. Male offspring alcohol-exposed sires were challenged with a high-fat diet molecular pathways controlling glucose assayed for LXR-induced alterations. Similar to findings studies employing LXR agonists found male display resistance diet-induced obesity improved when diet. This adaptation is mediated by LXRα trans-repression inflammatory cytokines, releasing IKKβ inhibition pathway. Interestingly, programmed increases expression liver-specific do not manifest pancreas or visceral fat. These identify key mediator long-term induced preconception use.

Language: Английский

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Exposure to drugs of abuse induce effects that persist across generations

International review of neurobiology, Journal Year: 2020, Volume and Issue: unknown, P. 217 - 277

Published: Sept. 30, 2020

Language: Английский

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Coincubation of sperm with epididymal extracellular vesicle preparations from chronic intermittent ethanol-treated mice is sufficient to impart anxiety-like and ethanol-induced behaviors to adult progeny

Alcohol, Journal Year: 2020, Volume and Issue: 87, P. 111 - 120

Published: May 21, 2020

Language: Английский

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