Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype

The contribution of the contents of spermatozoa to the development of the embryo is currently being considered wider than was previously thought. Recent findings point to the participation of epigenetic marks present in the retained histones of mature spermatozoa on embryo and fetal development. Here we created a novel conditional transgenic mouse that expresses lysine (K) demethylase 1a (Kdm1a) during spermatogenesis when the testicles are subjected to heat stress. Using these animals under these conditions we were able to reduce the methylation level of histone 3 at lysines 4 and 9 (H3K4 and H3K9, respectively) in mature spermatozoa. The offspring of these transgenic mice were followed for correct development and growth after birth. We found that the offspring of males expressing Kdm1a suffered 20% of reabsorptions at Day 15 after implantation (vs 0.3% in the control). In addition, 35% of the offspring sired by these males showed some kind of abnormality (suckling defects, lack of movement coordination, dropping forelimbs, abnormal body curvature, absence of eyes, gigantisms and neuromuscular defects) and 25% died before postnatal Day 21. Some abnormalities were maintained to adulthood. These results show that alteration of epigenetic marks present in the retained histones of mature spermatozoa affect fetal development and have phenotypic consequences in the newborn. © CSIRO 2017.

Saved in:
Bibliographic Details
Main Authors: Pérez-Cerezales, S., Ramos-Ibeas, P., Lopez-Cardona, A., Pericuesta, E., Fernandez-Gonzalez, R., Pintado, B., Gutiérrez-Adán, A.
Format: journal article biblioteca
Language:eng
Published: 2017
Online Access:http://hdl.handle.net/20.500.12792/3434
Tags: Add Tag
No Tags, Be the first to tag this record!
id dig-inia-es-20.500.12792-3434
record_format koha
spelling dig-inia-es-20.500.12792-34342020-12-15T09:52:29Z Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype Pérez-Cerezales, S. Ramos-Ibeas, P. Lopez-Cardona, A. Pericuesta, E. Fernandez-Gonzalez, R. Pintado, B. Gutiérrez-Adán, A. The contribution of the contents of spermatozoa to the development of the embryo is currently being considered wider than was previously thought. Recent findings point to the participation of epigenetic marks present in the retained histones of mature spermatozoa on embryo and fetal development. Here we created a novel conditional transgenic mouse that expresses lysine (K) demethylase 1a (Kdm1a) during spermatogenesis when the testicles are subjected to heat stress. Using these animals under these conditions we were able to reduce the methylation level of histone 3 at lysines 4 and 9 (H3K4 and H3K9, respectively) in mature spermatozoa. The offspring of these transgenic mice were followed for correct development and growth after birth. We found that the offspring of males expressing Kdm1a suffered 20% of reabsorptions at Day 15 after implantation (vs 0.3% in the control). In addition, 35% of the offspring sired by these males showed some kind of abnormality (suckling defects, lack of movement coordination, dropping forelimbs, abnormal body curvature, absence of eyes, gigantisms and neuromuscular defects) and 25% died before postnatal Day 21. Some abnormalities were maintained to adulthood. These results show that alteration of epigenetic marks present in the retained histones of mature spermatozoa affect fetal development and have phenotypic consequences in the newborn. © CSIRO 2017. 2020-10-22T14:40:27Z 2020-10-22T14:40:27Z 2017 journal article http://hdl.handle.net/20.500.12792/3434 10.1071/RD15349 eng Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0/ open access
institution INIA ES
collection DSpace
country España
countrycode ES
component Bibliográfico
access En linea
databasecode dig-inia-es
tag biblioteca
region Europa del Sur
libraryname Biblioteca del INIA España
language eng
description The contribution of the contents of spermatozoa to the development of the embryo is currently being considered wider than was previously thought. Recent findings point to the participation of epigenetic marks present in the retained histones of mature spermatozoa on embryo and fetal development. Here we created a novel conditional transgenic mouse that expresses lysine (K) demethylase 1a (Kdm1a) during spermatogenesis when the testicles are subjected to heat stress. Using these animals under these conditions we were able to reduce the methylation level of histone 3 at lysines 4 and 9 (H3K4 and H3K9, respectively) in mature spermatozoa. The offspring of these transgenic mice were followed for correct development and growth after birth. We found that the offspring of males expressing Kdm1a suffered 20% of reabsorptions at Day 15 after implantation (vs 0.3% in the control). In addition, 35% of the offspring sired by these males showed some kind of abnormality (suckling defects, lack of movement coordination, dropping forelimbs, abnormal body curvature, absence of eyes, gigantisms and neuromuscular defects) and 25% died before postnatal Day 21. Some abnormalities were maintained to adulthood. These results show that alteration of epigenetic marks present in the retained histones of mature spermatozoa affect fetal development and have phenotypic consequences in the newborn. © CSIRO 2017.
format journal article
author Pérez-Cerezales, S.
Ramos-Ibeas, P.
Lopez-Cardona, A.
Pericuesta, E.
Fernandez-Gonzalez, R.
Pintado, B.
Gutiérrez-Adán, A.
spellingShingle Pérez-Cerezales, S.
Ramos-Ibeas, P.
Lopez-Cardona, A.
Pericuesta, E.
Fernandez-Gonzalez, R.
Pintado, B.
Gutiérrez-Adán, A.
Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype
author_facet Pérez-Cerezales, S.
Ramos-Ibeas, P.
Lopez-Cardona, A.
Pericuesta, E.
Fernandez-Gonzalez, R.
Pintado, B.
Gutiérrez-Adán, A.
author_sort Pérez-Cerezales, S.
title Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype
title_short Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype
title_full Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype
title_fullStr Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype
title_full_unstemmed Elimination of methylation marks at lysines 4 and 9 of histone 3 (H3K4 and H3K9) of spermatozoa alters offspring phenotype
title_sort elimination of methylation marks at lysines 4 and 9 of histone 3 (h3k4 and h3k9) of spermatozoa alters offspring phenotype
publishDate 2017
url http://hdl.handle.net/20.500.12792/3434
work_keys_str_mv AT perezcerezaless eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
AT ramosibeasp eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
AT lopezcardonaa eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
AT pericuestae eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
AT fernandezgonzalezr eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
AT pintadob eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
AT gutierrezadana eliminationofmethylationmarksatlysines4and9ofhistone3h3k4andh3k9ofspermatozoaaltersoffspringphenotype
_version_ 1758005079969890304