Aberrant spliceosome expression and altered alternative splicing events correlate with maturation deficiency in human oocytes

Cell Cycle. 2020 Sep;19(17):2182-2194. doi: 10.1080/15384101.2020.1799295. Epub 2020 Aug 11.

Abstract

Different strategies of ovarian stimulation are widely used in IVF to retrieve mature metaphase II (MII) oocytes for fertilization. On average, approximately 70% of recovered oocytes are mature, while personalized administration of hCG and/or GnRH agonist trigger and in vitro maturation (IVM) management can further improve the maturation rate. However, even under such conditions, a complete absence of oocyte maturation is still observed sporadically. The probable causes for such maturation-deficient (MD) oocytes - which arrest abnormally at metaphase I (MI) stage - are still under investigation. In the present study, using single-cell transcriptomic RNA sequencing (RNA-seq) and differential expression analysis, we showed that gene expression profiles were aberrant, and alternative splicing (AS) patterns were changed in MD oocytes when compared with normally mature (MN) oocytes. Gene ontology (GO) enrichment demonstrated that the differently expressed genes (DEGs) were mostly correlated with pre-mRNA splicing, RNA transportation, RNA processing, and mRNA regulation. Subsequently, analysis of AS events revealed that genes with altered AS patterns were primarily associated with metabolism and cell cycle. With these findings, we have demonstrated aberrant gene expression in complete maturation-deficient oocytes, and we propose that alterations in post-transcriptional regulation constitute a potential underlying mechanism governing oocyte maturation.

Keywords: Oocyte maturation deficiency; spliceosome; transcriptome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alternative Splicing / genetics*
  • Cell Cycle / genetics
  • Cell Differentiation / genetics*
  • Gene Ontology
  • Humans
  • Oocytes / cytology*
  • Oocytes / metabolism*
  • RNA Precursors / genetics
  • RNA Precursors / metabolism
  • Spliceosomes / metabolism*
  • Transcriptome

Substances

  • RNA Precursors

Grants and funding

This work received funding support from the under Grant Nos. 2018YFC1003702, 2016YFC1000601, and 2018YFC1004403; the National Natural Science Foundation of China under Grant Nos. 31800624 and 81501322; the Key Clinical Program of Peking University Third Hospital under Grant BYSY2017031; and the State Key Laboratory of Molecular Developmental Biology under Grant 2018-MDB-KF-16.