Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age

Female fertility is inversely correlated with maternal age due to a depletion of the oocyte pool and a reduction in oocyte developmental competence. Few studies have addressed the effect of maternal age on the human mature oocyte (MII) transcriptome, which is established during oocyte growth and mat...

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Autores: Llonch, Sílvia, Barragan, Montserrat, Nieto, Paula, Mallol, Anna, Elosua-Bayés, Marc, Lorden, Patricia, Ruiz, Sara, Zambelli, Filippo, Heyn, Holger, Vassena, Rita, Payer, Bernhard
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2021
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/47673
Acceso en línea:http://hdl.handle.net/10230/47673
http://dx.doi.org/10.1111/acel.13360
Access Level:acceso abierto
Palabra clave:Fecunditat humana
Esterilitat
Genètica
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network_name_str España
repository_id_str
dc.title.none.fl_str_mv Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
title Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
spellingShingle Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
Llonch, Sílvia
Fecunditat humana
Esterilitat
Genètica
title_short Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
title_full Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
title_fullStr Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
title_full_unstemmed Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
title_sort Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
dc.creator.none.fl_str_mv Llonch, Sílvia
Barragan, Montserrat
Nieto, Paula
Mallol, Anna
Elosua-Bayés, Marc
Lorden, Patricia
Ruiz, Sara
Zambelli, Filippo
Heyn, Holger
Vassena, Rita
Payer, Bernhard
author Llonch, Sílvia
author_facet Llonch, Sílvia
Barragan, Montserrat
Nieto, Paula
Mallol, Anna
Elosua-Bayés, Marc
Lorden, Patricia
Ruiz, Sara
Zambelli, Filippo
Heyn, Holger
Vassena, Rita
Payer, Bernhard
author_role author
author2 Barragan, Montserrat
Nieto, Paula
Mallol, Anna
Elosua-Bayés, Marc
Lorden, Patricia
Ruiz, Sara
Zambelli, Filippo
Heyn, Holger
Vassena, Rita
Payer, Bernhard
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Fecunditat humana
Esterilitat
Genètica
topic Fecunditat humana
Esterilitat
Genètica
description Female fertility is inversely correlated with maternal age due to a depletion of the oocyte pool and a reduction in oocyte developmental competence. Few studies have addressed the effect of maternal age on the human mature oocyte (MII) transcriptome, which is established during oocyte growth and maturation, however, the pathways involved remain unclear. Here, we characterize and compare the transcriptomes of a large cohort of fully grown germinal vesicle stage (GV) and in vitro matured (IVM-MII) oocytes from women of varying reproductive age. First, we identified two clusters of cells reflecting the oocyte maturation stage (GV and IVM-MII) with 4445 and 324 putative marker genes, respectively. Furthermore, we identified genes for which transcript representation either progressively increased or decreased with age. Our results indicate that the transcriptome is more affected by age in IVM-MII oocytes (1219 genes) than in GV oocytes (596 genes). In particular, we found that transcripts of genes involved in chromosome segregation and RNA splicing significantly increased representation with age, while genes related to mitochondrial activity showed a lower representation. Gene regulatory network analysis facilitated the identification of potential upstream master regulators of the genes involved in those biological functions. Our analysis suggests that advanced maternal age does not globally affect the oocyte transcriptome at GV or IVM-MII stages. Nonetheless, hundreds of genes displayed altered transcript representation, particularly in IVM-MII oocytes, which might contribute to the age-related quality decline in human oocytes.
publishDate 2021
dc.date.none.fl_str_mv 2021
2021
2021
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/47673
http://dx.doi.org/10.1111/acel.13360
url http://hdl.handle.net/10230/47673
http://dx.doi.org/10.1111/acel.13360
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv info:eu-repo/grantAgreement/EC/H2020/754422
info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley Open Access
publisher.none.fl_str_mv Wiley Open Access
dc.source.none.fl_str_mv reponame:Repositorio Digital de la UPF
instname:Universitat Pompeu Fabra
instname_str Universitat Pompeu Fabra
reponame_str Repositorio Digital de la UPF
collection Repositorio Digital de la UPF
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spelling Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by ageLlonch, SílviaBarragan, MontserratNieto, PaulaMallol, AnnaElosua-Bayés, MarcLorden, PatriciaRuiz, SaraZambelli, FilippoHeyn, HolgerVassena, RitaPayer, BernhardFecunditat humanaEsterilitatGenèticaFemale fertility is inversely correlated with maternal age due to a depletion of the oocyte pool and a reduction in oocyte developmental competence. Few studies have addressed the effect of maternal age on the human mature oocyte (MII) transcriptome, which is established during oocyte growth and maturation, however, the pathways involved remain unclear. Here, we characterize and compare the transcriptomes of a large cohort of fully grown germinal vesicle stage (GV) and in vitro matured (IVM-MII) oocytes from women of varying reproductive age. First, we identified two clusters of cells reflecting the oocyte maturation stage (GV and IVM-MII) with 4445 and 324 putative marker genes, respectively. Furthermore, we identified genes for which transcript representation either progressively increased or decreased with age. Our results indicate that the transcriptome is more affected by age in IVM-MII oocytes (1219 genes) than in GV oocytes (596 genes). In particular, we found that transcripts of genes involved in chromosome segregation and RNA splicing significantly increased representation with age, while genes related to mitochondrial activity showed a lower representation. Gene regulatory network analysis facilitated the identification of potential upstream master regulators of the genes involved in those biological functions. Our analysis suggests that advanced maternal age does not globally affect the oocyte transcriptome at GV or IVM-MII stages. Nonetheless, hundreds of genes displayed altered transcript representation, particularly in IVM-MII oocytes, which might contribute to the age-related quality decline in human oocytes.Work on this study in the laboratory of B.P. has been funded by the AXA research fund (AXA Chair in Risk prediction in age-related diseases), contributions from Clinica EUGIN (Identification of Epigenetic Effects of Ageing on Human Oocytes), the Spanish Ministry of Science, Innovation and Universities (BFU2017-88407-P), the Agencia Estatal de Investigación (AEI) (EUR2019-103817) and the Catalan Agència de Gestió d'Ajuts Universitaris i de Recerca (AGAUR, 2017 SGR 346). S.L. has received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 754422. We acknowledge support of the Spanish Ministry of Science and Innovation through the Instituto de Salud Carlos III, to the EMBL partnership and to the Co-financing with funds from the European Regional Development Fund (FEDER) (Programa Operativo FEDER Plurirregional de España (POPE) 2014-2020). We also acknowledge support of the Centro de Excelencia Severo Ochoa and the Generalitat de Catalunya through the CERCA Programme, the Departament de Salut and Departament d'Empresa i Coneixement and through the Secretaria d'Universitats i Recerca for the Co-financing with FEDER funds (Programa Operatiu FEDER de Catalunya 2014-2020). Furthermore, this study has been supported by intramural funding of Clinica EUGIN to R.V.Wiley Open Access202120212021info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/47673http://dx.doi.org/10.1111/acel.13360reponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésinfo:eu-repo/grantAgreement/EC/H2020/754422info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P© 2021 Sílvia Llonch et al. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly citedhttps://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/476732026-06-12T07:21:37Z
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