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

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  • dc.contributor.author Llonch, Sílvia
  • dc.contributor.author Barragan, Montserrat
  • dc.contributor.author Nieto, Paula
  • dc.contributor.author Mallol, Anna
  • dc.contributor.author Elosua-Bayés, Marc
  • dc.contributor.author Lorden, Patricia
  • dc.contributor.author Ruiz, Sara
  • dc.contributor.author Zambelli, Filippo
  • dc.contributor.author Heyn, Holger
  • dc.contributor.author Vassena, Rita
  • dc.contributor.author Payer, Bernhard
  • dc.date.accessioned 2021-05-28T06:24:21Z
  • dc.date.available 2021-05-28T06:24:21Z
  • dc.date.issued 2021
  • dc.description.abstract 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.
  • dc.description.sponsorship 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.
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Llonch S, Barragán M, Nieto P, Mallol A, Elosua-Bayes M, Lorden P. Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age. Aging Cell. 2021 May;20(5):e13360. DOI: 10.1111/acel.13360
  • dc.identifier.doi http://dx.doi.org/10.1111/acel.13360
  • dc.identifier.issn 1474-9718
  • dc.identifier.uri http://hdl.handle.net/10230/47673
  • dc.language.iso eng
  • dc.publisher Wiley Open Access
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/754422
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-88407-P
  • dc.rights © 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 cited
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by/4.0/
  • dc.subject.other Fecunditat humana
  • dc.subject.other Esterilitat
  • dc.subject.other Genètica
  • dc.title Single human oocyte transcriptome analysis reveals distinct maturation stage-dependent pathways impacted by age
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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