Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer

Abstract The advent of assisted reproductive technologies (ART) in mammals involved an extraordinary change in the environment where the beginning of a new organism takes place. Under in vitro conditions, in which ART is currently being performed, it likely fails to mimic optimal in vivo conditions....

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Ximo Garcia-Dominguez, Francisco Marco-Jiménez, David S. Peñaranda, Gianfranco Diretto, Víctor García-Carpintero, Joaquín Cañizares, José S. Vicente
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6afd09899d894ad28eeec3e8babd6fe7
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:6afd09899d894ad28eeec3e8babd6fe7
record_format	dspace
spelling	oai:doaj.org-article:6afd09899d894ad28eeec3e8babd6fe72021-12-02T15:39:58ZLong-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer10.1038/s41598-020-68195-92045-2322https://doaj.org/article/6afd09899d894ad28eeec3e8babd6fe72020-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-68195-9https://doaj.org/toc/2045-2322Abstract The advent of assisted reproductive technologies (ART) in mammals involved an extraordinary change in the environment where the beginning of a new organism takes place. Under in vitro conditions, in which ART is currently being performed, it likely fails to mimic optimal in vivo conditions. This suboptimal environment could mediate in the natural developmental trajectory of the embryo, inducing lasting effects until later life stages that may be inherited by subsequent generations (transgenerational effects). Therefore, we evaluated the potential transgenerational effects of embryo exposure to the cryopreservation-transfer procedure in a rabbit model on the offspring phenotype, molecular physiology of the liver (transcriptome and metabolome) and reproductive performance during three generations (F1, F2 and F3). The results showed that, compared to naturally-conceived animals (NC group), progeny generated after embryo exposure to the cryopreservation-transfer procedure (VT group) exhibited lower body growth, which incurred lower adult body weight in the F1 (direct effects), F2 (intergenerational effects) and F3 (transgenerational effects) generations. Furthermore, VT animals showed intergenerational effects on heart weight and transgenerational effects on liver weight. The RNA-seq data of liver tissue revealed 642 differentially expressed transcripts (DETs) in VT animals from the F1 generation. Of those, 133 were inherited from the F2 and 120 from the F3 generation. Accordingly, 151, 190 and 159 differentially accumulated metabolites (DAMs) were detected from the F1, F2 and F3, respectively. Moreover, targeted metabolomics analysis demonstrated that transgenerational effects were mostly presented in the non-polar fraction. Functional analysis of molecular data suggests weakened zinc and fatty acid metabolism across the generations, associated with alterations in a complex molecular network affecting global hepatic metabolism that could be associated with the phenotype of VT animals. However, these VT animals showed proper reproductive performance, which verified a functional health status. In conclusion, our results establish the long-term transgenerational effects following a vitrified embryo transfer procedure. We showed that the VT phenotype could be the result of the manifestation of embryonic developmental plasticity in response to the stressful conditions during ART procedures.Ximo Garcia-DominguezFrancisco Marco-JiménezDavid S. PeñarandaGianfranco DirettoVíctor García-CarpinteroJoaquín CañizaresJosé S. VicenteNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-15 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ximo Garcia-Dominguez Francisco Marco-Jiménez David S. Peñaranda Gianfranco Diretto Víctor García-Carpintero Joaquín Cañizares José S. Vicente Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
description	Abstract The advent of assisted reproductive technologies (ART) in mammals involved an extraordinary change in the environment where the beginning of a new organism takes place. Under in vitro conditions, in which ART is currently being performed, it likely fails to mimic optimal in vivo conditions. This suboptimal environment could mediate in the natural developmental trajectory of the embryo, inducing lasting effects until later life stages that may be inherited by subsequent generations (transgenerational effects). Therefore, we evaluated the potential transgenerational effects of embryo exposure to the cryopreservation-transfer procedure in a rabbit model on the offspring phenotype, molecular physiology of the liver (transcriptome and metabolome) and reproductive performance during three generations (F1, F2 and F3). The results showed that, compared to naturally-conceived animals (NC group), progeny generated after embryo exposure to the cryopreservation-transfer procedure (VT group) exhibited lower body growth, which incurred lower adult body weight in the F1 (direct effects), F2 (intergenerational effects) and F3 (transgenerational effects) generations. Furthermore, VT animals showed intergenerational effects on heart weight and transgenerational effects on liver weight. The RNA-seq data of liver tissue revealed 642 differentially expressed transcripts (DETs) in VT animals from the F1 generation. Of those, 133 were inherited from the F2 and 120 from the F3 generation. Accordingly, 151, 190 and 159 differentially accumulated metabolites (DAMs) were detected from the F1, F2 and F3, respectively. Moreover, targeted metabolomics analysis demonstrated that transgenerational effects were mostly presented in the non-polar fraction. Functional analysis of molecular data suggests weakened zinc and fatty acid metabolism across the generations, associated with alterations in a complex molecular network affecting global hepatic metabolism that could be associated with the phenotype of VT animals. However, these VT animals showed proper reproductive performance, which verified a functional health status. In conclusion, our results establish the long-term transgenerational effects following a vitrified embryo transfer procedure. We showed that the VT phenotype could be the result of the manifestation of embryonic developmental plasticity in response to the stressful conditions during ART procedures.
format	article
author	Ximo Garcia-Dominguez Francisco Marco-Jiménez David S. Peñaranda Gianfranco Diretto Víctor García-Carpintero Joaquín Cañizares José S. Vicente
author_facet	Ximo Garcia-Dominguez Francisco Marco-Jiménez David S. Peñaranda Gianfranco Diretto Víctor García-Carpintero Joaquín Cañizares José S. Vicente
author_sort	Ximo Garcia-Dominguez
title	Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
title_short	Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
title_full	Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
title_fullStr	Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
title_full_unstemmed	Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
title_sort	long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/6afd09899d894ad28eeec3e8babd6fe7
work_keys_str_mv	AT ximogarciadominguez longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer AT franciscomarcojimenez longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer AT davidspenaranda longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer AT gianfrancodiretto longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer AT victorgarciacarpintero longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer AT joaquincanizares longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer AT josesvicente longtermandtransgenerationalphenotypictranscriptionalandmetaboliceffectsinrabbitmalesbornfollowingvitrifiedembryotransfer
_version_	1718385878051586048

Long-term and transgenerational phenotypic, transcriptional and metabolic effects in rabbit males born following vitrified embryo transfer

Ejemplares similares