NDLI: Single-cell RNA sequencing of human oocytes reveals a differential transcriptomic profile associated with agar-like zona pellucida

Content Provider	Springer Nature : BioMed Central
Author	Zhang, Xiangyang Shi, Senlin Wan, Ying Song, Wenyan Jin, Haixia Sun, Yingpu
Abstract	Background Agar-like zona pellucida (ZP) is the most common type of abnormal ZP, and is one of the causes of low fertility or infertility. However, the molecular mechanism of agar-like ZP is unclear. Single-cell RNA-sequencing (scRNA-seq) analysis was used to assess the cellular and molecular landscape of oocytes with agar-like ZP. Methods Human metaphase I (MI) oocytes were collected from four patients with agar-like ZP and four healthy donors. Total RNA was isolated, cDNA was synthesized, and libraries were generated and subsequently sequenced on a HiSeq 2500 instrument. The scRNA-seq data were analyzed with R software. Results We identified 1320 genes that were differentially expressed between agar-like ZP oocytes and healthy donor oocytes. Gene Ontology term enrichment results showed that the genes downregulated in agar-like ZP oocytes were significantly related to extracellular matrix organization, while the genes upregulated in agar-like ZP oocytes were significantly related to the regulation of response to DNA damage stimulus. The Kyoto Encyclopedia of Genes and Genomes enrichment results showed that genes were enriched in the ECM-receptor interaction pathway and focal adhesion pathway. Other signaling pathways important in oocyte development were also enriched, such as PI3K-Akt. Differential expression analysis identified UBC, TLR4, RELA, ANXA5, CAV1, KPNA2, CCNA2, ACTA2, FYN and ITGB3 as genetic markers of oocytes with agar-like ZP. Conclusions Our findings suggest that agar-like ZP oocytes exhibit significant downregulation of genes involved in the ECM-receptor interaction signaling pathway and focal adhesion pathway, which could lead to aberrant ZP formation, while the upregulated genes were significantly related to regulation of the response to DNA damage stimulus. Agar-like ZP formation may interfere with the normal exchange of signals between oocytes and perivitelline granulosa cells, thereby preventing cumulus cells from participating in oocyte DNA damage repair and causing MI arrest.
Related Links	https://ovarianresearch.biomedcentral.com/counter/pdf/10.1186/s13048-024-01463-8.pdf
Ending Page	10
Page Count	10
Starting Page	1
File Format	HTM / HTML
ISSN	17572215
DOI	10.1186/s13048-024-01463-8
Journal	Journal of Ovarian Research
Issue Number	1
Volume Number	17
Language	English
Publisher	BioMed Central
Publisher Date	2024-06-26
Access Restriction	Open
Subject Keyword	Gynecology Reproductive Medicine Human oocyte Agar-like zona pellucida scRNA-seq Transcriptomic analysis
Content Type	Text
Resource Type	Article
Subject	Oncology Obstetrics and Gynecology
Journal Impact Factor	3.8/2023
5-Year Journal Impact Factor	4.2/2023

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