PMID- 33554756 OWN - NLM STAT- MEDLINE DCOM- 20220316 LR - 20220531 IS - 1531-2267 (Electronic) IS - 1094-8341 (Print) IS - 1094-8341 (Linking) VI - 53 IP - 4 DP - 2021 Apr 1 TI - Shared aspects of mRNA expression associated with oocyte maturation failure in humans and rhesus monkeys indicating compromised oocyte quality. PG - 137-149 LID - 10.1152/physiolgenomics.00155.2020 [doi] AB - Oocyte maturation failure observed in assisted reproduction technology (ART) cycles can limit the number of quality oocytes obtained and present a pronounced barrier for some patients. The potential exists to use unmatured oocytes for ART through in vitro maturation. Understanding the molecular basis of oocyte maturation failure is pertinent to minimizing this loss of oocytes and considerations of whether such oocytes can be used safely for ART. We identified shared transcriptome abnormalities for rhesus monkey and human failed-to-mature (FTM) oocytes relative to healthy matured MII stage oocytes. We discovered that, although the number of shared affected genes was comparatively small, FTM oocytes in both species shared effects for several pathways and functions, including predicted activation of oxidative phosphorylation (OxPhos) with additional effects on mitochondrial function, lipid metabolism, transcription, nucleotide excision repair, endoplasmic reticulum stress, unfolded protein response, and cell viability. RICTOR emerged as a prominent upstream regulator with predicted inhibition across all analyses. Alterations in KDM5A, MTOR, MTORC1, INSR, CAB39L, and STK11 activities were implicated along with RICTOR in modulating mitochondrial activity and OxPhos. Defects in cell cycle progression were not a prominent feature of FTM oocytes. These results identify a common set of transcriptome abnormalities associated with oocyte maturation failure. While our results do not demonstrate causality, they indicate that fundamental aspects of cellular function are abnormal in FTM oocytes and raise significant concerns about the potential risks of using FTM oocytes for ART. FAU - Ruebel, Meghan L AU - Ruebel ML AUID- ORCID: 0000-0003-4303-1491 AD - Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan. FAU - Zambelli, Filippo AU - Zambelli F AD - Clinica EUGIN, Barcelona, Spain. FAU - Schall, Peter Z AU - Schall PZ AD - Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan. FAU - Barragan, Montserrat AU - Barragan M AD - Clinica EUGIN, Barcelona, Spain. FAU - VandeVoort, Catherine A AU - VandeVoort CA AD - California National Primate Research Center, University of California, Davis, California. AD - Department of Obstetrics and Gynecology, University of California, Davis, California. FAU - Vassena, Rita AU - Vassena R AD - Clinica EUGIN, Barcelona, Spain. FAU - Latham, Keith E AU - Latham KE AUID- ORCID: 0000-0003-1206-9059 AD - Department of Animal Science and Reproductive and Developmental Sciences Program, Michigan State University, East Lansing, Michigan. LA - eng GR - R24 OD012221/OD/NIH HHS/United States GR - T32HD087166/HD/NICHD NIH HHS/United States GR - T32 HD087166/HD/NICHD NIH HHS/United States GR - P51 OD011107/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210208 PL - United States TA - Physiol Genomics JT - Physiological genomics JID - 9815683 RN - 0 (RNA, Messenger) SB - IM MH - Animals MH - Humans MH - *In Vitro Oocyte Maturation Techniques/methods MH - Macaca mulatta/genetics MH - Mitochondria/metabolism MH - *Oocytes/metabolism MH - RNA, Messenger/metabolism PMC - PMC8083967 OTO - NOTNLM OT - meiosis OT - mitochondria OT - oocyte maturation OT - oxidative phosphorylation OT - transcriptome COIS- No conflicts of interest, financial or otherwise, are declared by the authors. EDAT- 2021/02/09 06:00 MHDA- 2022/03/22 06:00 PMCR- 2022/04/01 CRDT- 2021/02/08 08:42 PHST- 2021/02/09 06:00 [pubmed] PHST- 2022/03/22 06:00 [medline] PHST- 2021/02/08 08:42 [entrez] PHST- 2022/04/01 00:00 [pmc-release] AID - PG-00155-2020 [pii] AID - 10.1152/physiolgenomics.00155.2020 [doi] PST - ppublish SO - Physiol Genomics. 2021 Apr 1;53(4):137-149. doi: 10.1152/physiolgenomics.00155.2020. Epub 2021 Feb 8.