Paternal alcohol exposure and dental-facial anomalies in offspring. Reply.

Thomas, Kara N.; Derrico, Destani D.; Golding, Michael C.

doi:10.1172/jci174216

Cited by 3 publications

(1 citation statement)

References 4 publications

(6 reference statements)

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“…16,17 Using a mouse model, our group has demonstrated that chronic preconception paternal alcohol exposures induce dose-dependent changes in placental patterning, defects in craniofacial development, and long-term effects on postnatal glucose homeostasis. [31][32][33][34][35][36][37][38][39][40] In these previous studies, we did not observe any differences in sperm count, morphology, or offspring litter size. [31][32][33]35,37,39 However, using an in vitro fertilization (IVF) system to model the impacts of paternal alcohol use on early embryonic development, we observed that chronic ethanol exposures reduce embryo development and pregnancy success rates in a dose-dependent manner.…”

Section: Introductioncontrasting

confidence: 41%

Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction

Roach,

Bhadsavle,

Higgins

et al. 2023

Andrology

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BackgroundChronic preconception paternal alcohol use adversely modifies the sperm epigenome, inducing fetoplacental and craniofacial growth defects in the offspring of exposed males. A crucial outstanding question in the field of paternal epigenetic inheritance concerns the resilience of the male germline and its capacity to recover and correct sperm‐inherited epigenetic errors after stressor withdrawal.ObjectivesWe set out to determine if measures of the sperm‐inherited epigenetic program revert to match the control treatment 1 month after withdrawing the daily alcohol treatments.Materials and methodsUsing a voluntary access model, we exposed C57BL/6J males to 6% or 10% alcohol for 10 weeks, withdrew the alcohol treatments for 4 weeks, and used RNA sequencing to examine gene expression patterns in the caput section of the epididymis. We then compared the abundance of sperm small RNA species between treatments.ResultsIn the caput section of the epididymis, chronic alcohol exposure induced changes in the transcriptional control of genetic pathways related to the mitochondrial function, oxidative phosphorylation, and the generalized stress response (EIF2 signaling). Subsequent analysis identified region‐specific, alcohol‐induced changes in mitochondrial DNA copy number across the epididymis, which correlated with increases in the mitochondrial DNA content of alcohol‐exposed sperm. Notably, in the corpus section of the epididymis, increases in mitochondrial DNA copy number persisted 1 month after alcohol cessation. Analysis of sperm noncoding RNAs between control and alcohol‐exposed males 1 month after alcohol withdrawal revealed a ∼100‐fold increase in mir‐196a, a microRNA induced as part of the nuclear factor erythroid 2‐related factor 2 (Nrf2)‐driven cellular antioxidant response.Discussion and conclusionOur data reveal that alcohol‐induced epididymal mitochondrial dysfunction and differences in sperm noncoding RNA content persist after alcohol withdrawal. Further, differences in mir‐196a and sperm mitochondrial DNA copy number may serve as viable biomarkers of adverse alterations in the sperm‐inherited epigenetic program.

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Section: Introductioncontrasting

confidence: 41%

Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction

Roach,

Bhadsavle,

Higgins

et al. 2023

Andrology

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Maternal 129S1/SvImJ background attenuates the placental phenotypes induced by chronic paternal alcohol exposure

Bhadsavle,

Scaturro,

Golding

2024

Reproductive Toxicology

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Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model

Basel,

Bhadsavle,

Scaturro

et al. 2024

Aging and disease

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Although detrimental changes in mitochondrial morphology and function are widely described symptoms of fetal alcohol exposure, no studies have followed these mitochondrial deficits into adult life or determined if they predispose individuals with fetal alcohol spectrum disorders (FASDs) to accelerated biological aging. Here, we used a multiplex preclinical mouse model to compare markers of cellular senescence and age-related outcomes induced by maternal, paternal, and dual-parental alcohol exposures. We find that even in middle life (postnatal day 300), the adult offspring of alcohol-exposed parents exhibited significant increases in markers of stress-induced premature cellular senescence in the brain and liver, including an upregulation of cell cycle inhibitory proteins and increased senescence-associated β-galactosidase activity. Strikingly, in the male offspring, we observe an interaction between maternal and paternal alcohol use, with histological indicators of accelerated age-related liver disease in the dual-parental offspring exceeding those induced by either maternal or paternal alcohol use alone. Our studies indicate that chronic parental alcohol use causes enduring mitochondrial dysfunction in offspring, resulting in a reduced NAD+/NAHD ratio and altered expression of the NAD+-dependent deacetylases SIRT1 and SIRT3. These observations suggest that some aspects of FASDs may be linked to accelerated aging due to programmed changes in the regulation of mitochondrial function and cellular bioenergetics.

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Paternal alcohol exposure and dental-facial anomalies in offspring. Reply.

Cited by 3 publications

References 4 publications

Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction

Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction

Maternal 129S1/SvImJ background attenuates the placental phenotypes induced by chronic paternal alcohol exposure

Parental Alcohol Exposures Associate with Lasting Mitochondrial Dysfunction and Accelerated Aging in a Mouse Model

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