Abstract:
STUDY QUESTION:Which different pathways and functions are altered in rhesus monkey oocytes that fail to mature after an ovulatory stimulus? SUMMARY ANSWER:Failed to mature (FTM) oocytes complete a large portion of the transition in transcriptome composition associated with normal maturation, but also manifest numerous differences that indicate incomplete transcriptional repression and cytoplasmic maturation affecting multiple processes. WHAT IS KNOWN ALREADY:Oocyte maturation defects contribute to unexplained female infertility. Failure of some oocytes to undergo germinal vesicle breakdown or progress to second meiotic metaphase in response to an ovulatory stimulus can limit the number of high quality oocytes available for ART. STUDY DESIGN, SIZE, DURATION:The transcriptome of rhesus monkey oocytes that failed to mature (FTM; n = 11, 5 donors) in response to an ovulatory stimulus in vivo was compared to those of normal germinal vesicle stage (GV, n = 7, 2 donors) and metaphase II stage (MII, n = 7, 5 donors) oocytes by RNA-sequencing (RNAseq). PARTICIPANTS/MATERIALS, SETTING, METHODS:Female rhesus monkeys of normal breeding age (6-12 years old) and with regular menstrual cycles were used. Animals underwent a controlled ovarian stimulation protocol for the collection of oocytes by ultrasound-guided needle aspiration of follicles. MAIN RESULTS AND THE ROLE OF CHANCE:We obtained a high quality RNAseq dataset consisting of n = 7, n = 7, and n = 11 libraries for normal GV, normal MII and FTM oocytes, respectively. Total reads acquired were an average of 34 million for each GV sample, 41 million for each FTM sample and 59 million for each MII oocyte sample. Approximately 44% of the total reads were exonic reads that successfully aligned to the rhesus monkey genome as unique non-rRNA gene transcript sequences, providing high depth of coverage. Approximately 44% of the mRNAs that undergo changes in abundance during normal maturation display partial modulations to intermediate abundances, and 9.2% fail to diverge significantly from GV stage oocytes. Additionally, a small group of mRNAs are grossly mis-regulated in the FTM oocyte. Differential expression was seen for mRNAs associated with mitochondrial functions, fatty acid beta oxidation, lipid accumulation, meiosis, zona pellucida formation, Hippo pathway signaling, and maternal mRNA regulation. A deficiency DNA methyltransferase one mRNA expression indicates a potential defect in transcriptional silencing. LARGE SCALE DATA:All RNAseq data are published in the Gene Expression Omnibus Database (GSE112536). LIMITATIONS, REASONS FOR CAUTION:These results do not establish cause of maturation failure but reveal novel correlates of incompetence to mature. Transcriptome studies likely do not capture all post-transcriptional or post-translational events that inhibit maturation, but do reveal mRNA expression changes that lie downstream of such events or that are related to effects on upstream regulators. The use of an animal model allows the study of oocyte maturation failure independent of covariates and confounders, such as pre-existing conditions of the female, which is a significant concern in human studies. Depending on the legislation, it may not be possible to collect and study oocytes from healthy women; and using surplus oocytes from patients undergoing ART may introduce confounders that vary from case to case. FTM oocytes were at various stages of meiotic progression, so correlates of specific times of arrest are not revealed. All the FTM oocytes failed to respond appropriately to an ovulatory stimulus in vivo. Therefore, this analysis informs us about common transcriptome features associated with meiotic incompetence. WIDER IMPLICATIONS OF THE FINDINGS:These results reveal that some diagnostic markers of oocyte quality may not reflect developmental competence because even meiotically incompetent oocytes display many normal gene expression features. The results also reveal potential mechanisms by which maternal and environmental factors may impact transcriptional repression and cytoplasmic maturation, and prevent oocyte maturation. STUDY FUNDING/COMPETING INTEREST(S):This work was supported by grants from the National Institutes of Health Office of Research Infrastructure Programs Division of Comparative Medicine Grants R24 [OD012221 to K.E.L., OD011107/RR00169 (California National Primate Research Center), and OD010967/RR025880 to C.A.V.]; the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under the award number T32HD087166; MSU AgBioResearch, Michigan State University. Authors have nothing to disclose.
journal_name
Mol Hum Reprodjournal_title
Molecular human reproductionauthors
Ruebel ML,Schall PZ,Midic U,Vincent KA,Goheen B,VandeVoort CA,Latham KEdoi
10.1093/molehr/gay032subject
Has Abstractpub_date
2018-10-01 00:00:00pages
478-494issue
10eissn
1360-9947issn
1460-2407pii
5065379journal_volume
24pub_type
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/5.11.995
更新日期:1999-11-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章,评审
doi:10.1093/molehr/4.8.739
更新日期:1998-08-01 00:00:00
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journal_title:Molecular human reproduction
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journal_title:Molecular human reproduction
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更新日期:1999-04-01 00:00:00
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pub_type: 杂志文章,评审
doi:10.1093/molehr/3.4.321
更新日期:1997-04-01 00:00:00
abstract::Type I inositol 1,4,5-trisphosphate-sensitive receptors (InsP(3)R) are expressed in human oocytes and may be involved in operating the Ca(2+) release triggered by the fertilizing sperm. This study examines the contribution of type I InsP(3)R in operating Ca(2+) release in human oocytes secondary to InsP(3) itself, usi...
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pub_type: 杂志文章
doi:10.1093/molehr/8.10.912
更新日期:2002-10-01 00:00:00
abstract:STUDY QUESTION:Does a heterozygous mutation in AMHR2, identified in whole-exome sequencings (WES) of patients with primary ovarian insufficiency (POI), cause a defect in anti-Müllerian hormone (AMH) signaling? SUMMARY ANSWER:The I209N mutation at the adenosine triphosphate binding domain of AMHR2 exerts dominant negat...
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaz001
更新日期:2019-03-01 00:00:00
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journal_title:Molecular human reproduction
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pub_type: 杂志文章
doi:10.1093/molehr/gah202
更新日期:2005-07-01 00:00:00
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doi:10.1093/molehr/gaaa082
更新日期:2021-01-22 00:00:00
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journal_title:Molecular human reproduction
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更新日期:2000-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/molehr/gag019
更新日期:2003-03-01 00:00:00
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pub_type: 杂志文章
doi:10.1093/molehr/gal033
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pub_type: 杂志文章
doi:10.1093/molehr/5.11.1066
更新日期:1999-11-01 00:00:00
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pub_type: 杂志文章
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更新日期:2002-09-01 00:00:00
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journal_title:Molecular human reproduction
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更新日期:2016-03-01 00:00:00
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journal_title:Molecular human reproduction
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更新日期:2015-10-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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更新日期:2004-05-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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更新日期:1997-09-01 00:00:00
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journal_title:Molecular human reproduction
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更新日期:2004-11-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/3.11.953
更新日期:1997-11-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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更新日期:2006-12-01 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
doi:10.1093/molehr/gaaa080
更新日期:2020-12-18 00:00:00
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journal_title:Molecular human reproduction
pub_type: 杂志文章
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更新日期:2017-12-01 00:00:00