{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:10:48Z","timestamp":1777392648044,"version":"3.51.4"},"reference-count":71,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,12,3]],"date-time":"2023-12-03T00:00:00Z","timestamp":1701561600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000888","name":"W. M. 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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\u2010inherited epigenetic errors after stressor withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We set out to determine if measures of the sperm\u2010inherited epigenetic program revert to match the control treatment 1 month after withdrawing the daily alcohol treatments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Using 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In 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\u2010specific, alcohol\u2010induced changes in mitochondrial DNA copy number across the epididymis, which correlated with increases in the mitochondrial DNA content of alcohol\u2010exposed 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\u2010exposed males 1 month after alcohol withdrawal revealed a \u223c100\u2010fold increase in mir\u2010196a, a microRNA induced as part of the nuclear factor erythroid 2\u2010related factor 2 (Nrf2)\u2010driven cellular antioxidant response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>Our data reveal that alcohol\u2010induced epididymal mitochondrial dysfunction and differences in sperm noncoding RNA content persist after alcohol withdrawal. Further, differences in mir\u2010196a and sperm mitochondrial DNA copy number may serve as viable biomarkers of adverse alterations in the sperm\u2010inherited epigenetic program.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13566","type":"journal-article","created":{"date-parts":[[2023,12,4]],"date-time":"2023-12-04T07:36:31Z","timestamp":1701675391000},"page":"1012-1023","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Alterations in sperm RNAs persist after alcohol cessation and correlate with epididymal mitochondrial dysfunction"],"prefix":"10.1111","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-8621","authenticated-orcid":false,"given":"Alexis N.","family":"Roach","sequence":"first","affiliation":[{"name":"Department of Veterinary Physiology &amp; Pharmacology, School of Veterinary Medicine and Biomedical Sciences Texas A&amp;M University, College Station  Texas 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