17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice

Abstract Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical natur...

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Main Authors: L. Ded, E. Zatecka-Lanska, E. Vaculikova, M. Frolikova, O. Sanovec, V. Palenikova, O. Simonik, A. Dorosh, H. Margaryan, F. Elzeinova, A. Kubatova, J. Peknicova, A. Paradowska-Dogan, K. Steger, K. Komrskova
Format: Article
Language:English
Published: BMC 2024-11-01
Series:Reproductive Biology and Endocrinology
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Online Access:https://doi.org/10.1186/s12958-024-01307-6
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author L. Ded
E. Zatecka-Lanska
E. Vaculikova
M. Frolikova
O. Sanovec
V. Palenikova
O. Simonik
A. Dorosh
H. Margaryan
F. Elzeinova
A. Kubatova
J. Peknicova
A. Paradowska-Dogan
K. Steger
K. Komrskova
author_facet L. Ded
E. Zatecka-Lanska
E. Vaculikova
M. Frolikova
O. Sanovec
V. Palenikova
O. Simonik
A. Dorosh
H. Margaryan
F. Elzeinova
A. Kubatova
J. Peknicova
A. Paradowska-Dogan
K. Steger
K. Komrskova
author_sort L. Ded
collection DOAJ
description Abstract Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.
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spelling doaj-art-de470ece8aff438a9cf6aa04af3a28ad2024-11-10T12:47:21ZengBMCReproductive Biology and Endocrinology1477-78272024-11-0122111310.1186/s12958-024-01307-617α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in miceL. Ded0E. Zatecka-Lanska1E. Vaculikova2M. Frolikova3O. Sanovec4V. Palenikova5O. Simonik6A. Dorosh7H. Margaryan8F. Elzeinova9A. Kubatova10J. Peknicova11A. Paradowska-Dogan12K. Steger13K. Komrskova14Laboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVDepartment of Urology, Pediatric Urology and Andrology, Molecular Andrology, Biomedical Research Center of the Justus-Liebig UniversityLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVLaboratory of Reproductive Biology, Institute of Biotechnology of the Czech Academy of Sciences, BIOCEVAbstract Spermatogenesis starts with the onset of puberty within the seminiferous epithelium of the testes. It is a complex process under intricate control of the endocrine system. Physiological regulations by steroid hormones in general and by estrogens in particular are due to their chemical nature prone to be disrupted by exogenous factors acting as endocrine disruptors (EDs). 17α-Ethynylestradiol (EE2) is an environmental pollutant with a confirmed ED activity and a well-known effect on spermatogenesis and chromatin remodeling in haploid germ cells. The aim of our study was to assess possible effects of two doses (2.5ng/ml; 2.5 μg/ml) of EE2 on both histone-to-protamine exchange and epigenetic profiles during spermatogenesis performing a multi/transgenerational study in mice. Our results demonstrated an impaired histone-to-protamine exchange with a significantly higher histone retention in sperm nuclei of exposed animals, when this process was accompanied by the changes of histone post-translational modifications (PTMs) abundancies with a prominent effect on H3K9Ac and partial changes in protamine 1 promoter methylation status. Furthermore, individual changes in molecular phenotypes were partially transmitted to subsequent generations, when no direct trans-generational effect was observed. Finally, the uncovered specific localization of the histone retention in sperm nuclei and their specific PTMs profile after EE2 exposure may indicate an estrogenic effect on sperm motility and early embryonic development via epigenetic mechanisms.https://doi.org/10.1186/s12958-024-01307-617α-EthynylestradiolEE2Endocrine disruptorsPost-translational modificationsTestisSperm
spellingShingle L. Ded
E. Zatecka-Lanska
E. Vaculikova
M. Frolikova
O. Sanovec
V. Palenikova
O. Simonik
A. Dorosh
H. Margaryan
F. Elzeinova
A. Kubatova
J. Peknicova
A. Paradowska-Dogan
K. Steger
K. Komrskova
17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice
Reproductive Biology and Endocrinology
17α-Ethynylestradiol
EE2
Endocrine disruptors
Post-translational modifications
Testis
Sperm
title 17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice
title_full 17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice
title_fullStr 17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice
title_full_unstemmed 17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice
title_short 17α-Ethynylestradiol alters testicular epigenetic profiles and histone-to-protamine exchange in mice
title_sort 17α ethynylestradiol alters testicular epigenetic profiles and histone to protamine exchange in mice
topic 17α-Ethynylestradiol
EE2
Endocrine disruptors
Post-translational modifications
Testis
Sperm
url https://doi.org/10.1186/s12958-024-01307-6
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