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Transcriptomic responses of cumulus granulosa cells to SARS-CoV-2 infection during controlled ovarian stimulation

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Abstract

Cumulus granulosa cells (CGCs) play a crucial role in follicular development, but so far, no research has explored the impact of SARS-CoV-2 infection on ovarian function from the perspective of CGCs. In the present study, we compared the cycle outcomes between infected and uninfected female patients undergoing controlled ovarian stimulation, performed bulk RNA-sequencing of collected CGCs, and used bioinformatic methods to explore transcriptomic changes. The results showed that women with SARS-CoV-2 infection during stimulation had significantly lower number of oocytes retrieved and follicle-oocyte index, while subsequent fertilization and embryo development were similar. CGCs were not directly infected by SARS-CoV-2, but exhibited dramatic differences in gene expression (156 up-regulated and 65 down-regulated). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses demonstrated a high enrichment in antiviral, immune and inflammatory responses with necroptosis. In addition, the pathways related to telomere organization and double strand break repair were significantly affected by infection in gene set enrichment analysis. Further weighted gene co-expression network analysis identified a key module associated with ovarian response traits, which was mainly enriched as a decrease of leukocyte chemotaxis and migration in CGCs. For the first time, our study describes how SARS-CoV-2 infection indirectly affects CGCs at the transcriptional level, which may impair oocyte-CGC crosstalk and consequently lead to poor ovarian response during fertility treatment.

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Data availability

The dataset analyzed during the current study has been submitted to the NCBI BioProject with accession number (PRJNA1003555).

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Acknowledgements

We are grateful to the LC-Bio Technology for assisting in sequencing and bioinformatic analysis.

Funding

This work was supported by the National Natural Science Foundation of China (82260315) and Natural Science Foundation of Jiangxi Province (20224BAB216025).

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Author notes

  1. Jialyu Huang, Zheng Fang, Xingwu Wu authors contributed equally to this work.

Authors and Affiliations

  1. Center for Reproductive Medicine, Jiangxi Branch of National Clinical Research Center for Obstetrics and Gynecology, Jiangxi Maternal and Child Health Hospital, Nanchang Medical College, 318 Bayi Avenue, Nanchang, 330006, China

    Jialyu Huang, Xingwu Wu, Leizhen Xia, Dingfei Xu, Ke Zhang, Qiqi Xie, Jia Chen, Peipei Liu, Qiongfang Wu, Jun Tan & Lifeng Tian

  2. Center for Reproductive Medicine, Department of Gynecology and Obstetrics, Tangdu Hospital, Air Force Medical University, Xi’an, China

    Zheng Fang

  3. Department of Clinical Medicine, School of Queen Mary, Nanchang University, Nanchang, China

    Yuxin Liu

  4. Reproductive and Genetic Hospital, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China

    Jiawei Wang

  5. Department of Oncology, Jiangxi Branch of National Clinical Research Center for Obstetrics and Gynecology, Jiangxi Maternal and Child Health Hospital, Nanchang Medical College, Nanchang, China

    Yufang Su

  6. Department of Physiology, Jiangxi Provincial Key Laboratory of Reproductive Physiology and Pathology, School of Basic Medical Sciences, Nanchang University, 461 Bayi Avenue, Nanchang, China

    Haibin Kuang

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  1. Jialyu Huang
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Contributions

J.H., L.T. and H.K. conceptualized and designed the study. X.W., J.C., and P.L. collected patient sample. L.X., D.X., K.Z. and Q.X. were responsible for clinical follow-up and data curation. X.W. and Z.F. performed the study experiments. Y.L., J.W. and Y.S. performed the statistical analyses. J.H. conducted computational bioinformatics analysis and wrote the original draft. J.T., H.K. and L.T. supervised the project administration and edited the manuscript. All authors reviewed the manuscript.

Corresponding authors

Correspondence to Jun Tan, Haibin Kuang or Lifeng Tian.

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The study was approved by the Reproductive Medicine Ethics Committee of Jiangxi Maternal and Child Health Hospital. All patients provided written informed contents for participation.

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The authors declare no competing interests.

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Huang, J., Fang, Z., Wu, X. et al. Transcriptomic responses of cumulus granulosa cells to SARS-CoV-2 infection during controlled ovarian stimulation. Apoptosis 29, 649–662 (2024). https://doi.org/10.1007/s10495-024-01942-9

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