Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol

Abstract It is well established that maternal lifestyle during pregnancy and lactation affects the intrauterine programming of F1 offspring. However, despite the co-use of alcohol and nicotine is a common habit, the effects of exposure to both substances on the reproductive system of F1 male offspri...

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Autores principales:	Athareh Pabarja, Sepideh Ganjalikhan Hakemi, Elahe Musanejad, Massood Ezzatabadipour, Seyed Noureddin Nematollahi-Mahani, Ali Afgar, Mohammad Reza Afarinesh, Tahereh Haghpanah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97a371248fa44939b1d98b47c7a0c1a1
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spelling	oai:doaj.org-article:97a371248fa44939b1d98b47c7a0c1a12021-12-02T15:02:52ZGenetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol10.1038/s41598-021-91739-62045-2322https://doaj.org/article/97a371248fa44939b1d98b47c7a0c1a12021-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-91739-6https://doaj.org/toc/2045-2322Abstract It is well established that maternal lifestyle during pregnancy and lactation affects the intrauterine programming of F1 offspring. However, despite the co-use of alcohol and nicotine is a common habit, the effects of exposure to both substances on the reproductive system of F1 male offspring and the underlying mechanisms of developmental programming have not been investigated. The present study aimed to examine pre- and postnatal concurrent exposure to these substances on genetic and epigenetic alterations of sperm cells as well as testis properties of F1 offspring compared with exposure to each substance alone. Pregnant dams in the F0 generation randomly received normal saline, nicotine, ethanol, and combinations throughout full gestation and lactation periods. Sperm cells and testes of F1 male offspring were collected at postnatal day 90 for further experiments. High levels of sperm DNA fragmentation were observed in all exposed offspring. Regarding epigenetic alterations, there was a significant increase in the relative transcript abundance of histone deacetylase 1 and 2 in all exposed sperm cells. Moreover, despite a decrease in the expression level of DNA methyltransferase (DNMT) 3A, no marked differences were found in the expression levels of DNMT1 and 3B in any of the exposed sperm cells compared to non-exposed ones. Interestingly, combined exposure had less prominent effects relative to exposure to each substance alone. The changes in the testicular and sperm parameters were compatible with genetic and epigenetic alterations. However, MDA level as an oxidative stress indicator increased in all exposed pups, which may be responsible for such outputs. In conclusion, maternal co-exposure to these substances exhibited epigenotoxicity effects on germline cells of F1 male offspring, although these effects were less marked relative to exposure to each substance alone. These counteracting effects may be explained by cross-tolerance and probably less impairment of the antioxidant defense system.Athareh PabarjaSepideh Ganjalikhan HakemiElahe MusanejadMassood EzzatabadipourSeyed Noureddin Nematollahi-MahaniAli AfgarMohammad Reza AfarineshTahereh HaghpanahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Athareh Pabarja Sepideh Ganjalikhan Hakemi Elahe Musanejad Massood Ezzatabadipour Seyed Noureddin Nematollahi-Mahani Ali Afgar Mohammad Reza Afarinesh Tahereh Haghpanah Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
description	Abstract It is well established that maternal lifestyle during pregnancy and lactation affects the intrauterine programming of F1 offspring. However, despite the co-use of alcohol and nicotine is a common habit, the effects of exposure to both substances on the reproductive system of F1 male offspring and the underlying mechanisms of developmental programming have not been investigated. The present study aimed to examine pre- and postnatal concurrent exposure to these substances on genetic and epigenetic alterations of sperm cells as well as testis properties of F1 offspring compared with exposure to each substance alone. Pregnant dams in the F0 generation randomly received normal saline, nicotine, ethanol, and combinations throughout full gestation and lactation periods. Sperm cells and testes of F1 male offspring were collected at postnatal day 90 for further experiments. High levels of sperm DNA fragmentation were observed in all exposed offspring. Regarding epigenetic alterations, there was a significant increase in the relative transcript abundance of histone deacetylase 1 and 2 in all exposed sperm cells. Moreover, despite a decrease in the expression level of DNA methyltransferase (DNMT) 3A, no marked differences were found in the expression levels of DNMT1 and 3B in any of the exposed sperm cells compared to non-exposed ones. Interestingly, combined exposure had less prominent effects relative to exposure to each substance alone. The changes in the testicular and sperm parameters were compatible with genetic and epigenetic alterations. However, MDA level as an oxidative stress indicator increased in all exposed pups, which may be responsible for such outputs. In conclusion, maternal co-exposure to these substances exhibited epigenotoxicity effects on germline cells of F1 male offspring, although these effects were less marked relative to exposure to each substance alone. These counteracting effects may be explained by cross-tolerance and probably less impairment of the antioxidant defense system.
format	article
author	Athareh Pabarja Sepideh Ganjalikhan Hakemi Elahe Musanejad Massood Ezzatabadipour Seyed Noureddin Nematollahi-Mahani Ali Afgar Mohammad Reza Afarinesh Tahereh Haghpanah
author_facet	Athareh Pabarja Sepideh Ganjalikhan Hakemi Elahe Musanejad Massood Ezzatabadipour Seyed Noureddin Nematollahi-Mahani Ali Afgar Mohammad Reza Afarinesh Tahereh Haghpanah
author_sort	Athareh Pabarja
title	Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
title_short	Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
title_full	Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
title_fullStr	Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
title_full_unstemmed	Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
title_sort	genetic and epigenetic modifications of f1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/97a371248fa44939b1d98b47c7a0c1a1
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Genetic and epigenetic modifications of F1 offspring’s sperm cells following in utero and lactational combined exposure to nicotine and ethanol

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