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DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures

Cui-Ling Lu Xue-Ling Song Xiao-Ying Zheng Tian-Shu Song Xiao-Na Wang Jie Yan Rui Yang Rong Li Jie Qiao

Cui-Ling Lu, Xue-Ling Song, Xiao-Ying Zheng, Tian-Shu Song, Xiao-Na Wang, Jie Yan, Rui Yang, Rong Li, Jie Qiao. DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures[J]. 遗传学报, 2026, 53(1): 121-130. doi: 10.1016/j.jgg.2025.05.002
引用本文: Cui-Ling Lu, Xue-Ling Song, Xiao-Ying Zheng, Tian-Shu Song, Xiao-Na Wang, Jie Yan, Rui Yang, Rong Li, Jie Qiao. DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures[J]. 遗传学报, 2026, 53(1): 121-130. doi: 10.1016/j.jgg.2025.05.002
Cui-Ling Lu, Xue-Ling Song, Xiao-Ying Zheng, Tian-Shu Song, Xiao-Na Wang, Jie Yan, Rui Yang, Rong Li, Jie Qiao. DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures[J]. Journal of Genetics and Genomics, 2026, 53(1): 121-130. doi: 10.1016/j.jgg.2025.05.002
Citation: Cui-Ling Lu, Xue-Ling Song, Xiao-Ying Zheng, Tian-Shu Song, Xiao-Na Wang, Jie Yan, Rui Yang, Rong Li, Jie Qiao. DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures[J]. Journal of Genetics and Genomics, 2026, 53(1): 121-130. doi: 10.1016/j.jgg.2025.05.002

DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures

doi: 10.1016/j.jgg.2025.05.002
基金项目: 

This work was supported by funding from the National Natural Science Foundation of China (81971349 and 81300456). We are deeply grateful to Dr. Zhu-Qiang Zhang (Institute of Biophysics, Chinese Academy of Sciences) for his assistance with rewriting this paper and data analysis, thank Dr. Hong-Shan Guo (Zhejiang University School of Medicine) for his methylation-seq data of human oocyte maturation matured in vivo and technical guidance, and thank Dr. Wei Chen (Peking University Third Hospital) for his assistance with data analysis. Additionally, we thank all the doctors and nurses of the Reproductive Medical Centre of Peking University Third Hospital for their excellent assistance.

详细信息
    通讯作者:

    Cui-Ling Lu,E-mail:luclbj@ibp.ac.cn

    Rui Yang,E-mail:yrjeff@126.com

DNA methylation landscapes of in vitro matured oocytes retrieved during endoscopic gynaecological procedures

Funds: 

This work was supported by funding from the National Natural Science Foundation of China (81971349 and 81300456). We are deeply grateful to Dr. Zhu-Qiang Zhang (Institute of Biophysics, Chinese Academy of Sciences) for his assistance with rewriting this paper and data analysis, thank Dr. Hong-Shan Guo (Zhejiang University School of Medicine) for his methylation-seq data of human oocyte maturation matured in vivo and technical guidance, and thank Dr. Wei Chen (Peking University Third Hospital) for his assistance with data analysis. Additionally, we thank all the doctors and nurses of the Reproductive Medical Centre of Peking University Third Hospital for their excellent assistance.

  • 摘要: In vitro maturation (IVM) of human oocytes offers cost efficiency and minimal invasiveness, serving as a valuable supplementary tool in assisted reproduction for fertility preservation, ovarian hyperstimulation syndrome prevention, and other reproductive strategies. Despite its availability for three decades, the clinical use of IVM remains limited due to efficacy and safety concerns. This study examines the DNA methylation profile of IVM oocytes collected during laparoscopic/hysteroscopic surgeries compared to in vivo matured oocytes via reduced representation bisulfite sequencing. Results indicate IVM oocytes exhibit a higher global methylation level. Differentially methylated regions (DMRs) analysis reveals that the in vitro group displays more hypermethylated and fewer hypomethylated DMRs compared to the in vivo group. Additionally, the in vitro group exhibits a higher level of non-CpG methylation than the in vivo group. However, no significant correlation between methylation levels and transcriptional activity in these oocytes is found, especially for those specific imprinted genes or genes related to embryonic development. These findings shed light on the epigenetic landscape of IVM oocytes, contributing to the ongoing assessment of their clinical feasibility and safety in assisted reproduction.
  • Akalin, A., Kormaksson, M., Li, S., Garrett-Bakelman, F.E., Figueroa, M.E., Melnick, A., Mason, C.E., 2012. MethylKit: a comprehensive R package for the analysis of genome-wide DNA methylation profiles. Genome Biol. 13, R87.
    Berwanger, A.L., Finet, A., El Hachem, H., le Parco, S., Hesters, L., Grynberg, M., 2012. New trends in female fertility preservation: in vitro maturation of oocytes. Future Oncol. 8, 1567-1573.
    Borghol, N., Lornage, J., Blachere, T., Sophie Garret, A., Lefevre, A., 2006. Epigenetic status of the H19 locus in human oocytes following in vitro maturation. Genomics 87, 417-426.
    Cadenas, J., la Cour Poulsen, L., Mamsen, L.S., Andersen, C.Y., 2023. Future potential of IVM including fertility preservation. Fertil. Steril. 19, 550-559.
    Chen, W., Peng, Y., Ma, X., Kong, S., Tan, S., Wei, Y., Zhao, Y., Zhang, W., Wang, Y., Yan, L., Qiao, J., 2020. Integrated multi-omics reveal epigenomic disturbance of assisted reproductive technologies in human offspring. EBioMedicine 61, 103076.
    Chen, E.Y., Tan, C.M., Kou, Y., Duan, Q., Wang, Z., Meirelles, G.V., Clark, N.R., Maayan, A., 2013. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform. 14, 128.
    Chian, R.C., Gulekli, B., Buckett, W.M., Tan, S.L., 1999. Priming with human chorionic gonadotropin before retrieval of immature oocytes in women with infertility due to the polycystic ovary syndrome. N. Engl. J. Med. 341, 1624-1626.
    Chian, R.C., Uzelac, P.S., Nargund, G., 2013. In vitro maturation of human immature oocytes for fertility preservation. Fertil. Steril. 99, 1173-1181.
    Chian, R.C., Xu, C.L., Huang, J.Y., Ata, B., 2014. Obstetric outcomes and congenital abnormalities in infants conceived with oocytes matured in vitro. Facts Views Vis. Obgyn. 6, 15-18.
    Child, T.J., Abdul-Jalil, A.K., Gulekli, B., Tan, S.L., 2001. In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome. Fertil. Steril. 76, 936-942.
    Conti, M., Franciosi, F., 2018. Acquisition of oocyte competence to develop as an embryo: integrated nuclear and cytoplasmic events. Hum. Reprod. Update 24, 245-266.
    De Vos, M., Ortega-Hrepich, C., Albuz, F.K., Guzman, L., Polyzos, N.P., Smitz, J., Devroey, P., 2011. Clinical outcome of non-hCG-primed oocyte in vitro maturation treatment in patients with polycystic ovaries and polycystic ovary syndrome. Fertil. Steril. 96, 860-864.
    De Vos, M., Smitz, J., Thompson, J.G., Gilchrist, R.B., 2016. The definition of IVM is clear-variations need defining. Hum. Reprod. 31, 2411-2415.
    Denomme, M.M., Mann, M.R.W., 2013. Maternal control of genomic imprint maintenance. Reproductive BioMedicine Online 27, 629-636.
    Ducreux, B., Patrat, C., Trasler, J., Fauque, P., 2023. Transcriptomic integrity of human oocytes used in ARTs: technical and intrinsic factor effects. Hum. Reprod. Update 30, 26-47.
    Dvoran, M., Iyyappan, R., Masek, T., Pospisek, M., Kubelka, M., Susor, A., 2024. Assessment of active translation in cumulus-enclosed and denuded oocytes during standard in vitro maturation and early embryo development. Hum. Reprod. 39, 1752-1766.
    Fadini, R., Mignini Renzini, M., Dal Canto, M., Epis, A., Crippa, M., Caliari, I., Brigante, C., Coticchio, G., 2013. Oocyte in vitro maturation in normo-ovulatory women. Fertil. Steril. 99, 1162-1169.
    Gilchrist, R.B., Ho, T.M., De Vos, M., Sanchez, F., Romero, S., Ledger, W.L., Anckaert, E., Vuong, L.N., Smitz, J., 2023. A fresh start for IVM: capacitating the oocyte for development using pre-IVM. Hum. Reprod. Update 30, 3-25.
    Gilchrist, R.B., Smitz, J., 2023. Oocyte in vitro maturation: physiological basis and application to clinical practice. Fertil. Steril. 119, 524-539.
    Gu, H., Smith, Z.D., Bock, C., Boyle, P., Gnirke, A., Meissner, A., 2011. Preparation of reduced representation bisulfite sequencing libraries for genome-scale DNA methylation profiling. Nat. Protoc. 6, 468-481.
    Guo, Y., Cai, L., Liu, X., Ma, L., Zhang, H., Wang, B., Qi, Y., Liu, J., Diao, F., Sha, J., Guo, X., 2022. Single-cell quantitative proteomic analysis of human oocyte maturation revealed high heterogeneity in in vitro matured oocytes. Mol. Cell Proteomics 21, 100267.
    Guo, H., Zhu, P., Guo, F., Li, X., Wu, X., Fan, X., Wen, L., Tang, F., 2015. Profiling DNA methylome landscapes of mammalian cells with single-cell reduced-representation bisulfite sequencing. Nat. Protoc. 10, 645-659.
    Guo, H., Zhu, P., Wu, X., Li, X., Wen, L., Tang, F., 2013. Single-cell methylome landscapes of mouse embryonic stem cells and early embryos analyzed using reduced representation bisulfite sequencing. Genome Res. 23, 2126-2135.
    Heinz, S., Benner, C., Spann, N., Bertolino, E., Lin, Y.C., Laslo, P., Cheng, J.X., Murre, C., Singh, H., Glass, C.K., 2010. Simple combinations of lineage-determining transcription factors prime cis-regulatory elements required for macrophage and B cell identities. Mol. Cell 38, 576-589.
    Jones, G.M., Cram, D.S., Song, B., Magli, M.C., Gianaroli, L., Lacham-Kaplan, O., Findlay, J.K., Jenkin, G., Trounson, A.O., 2008. Gene expression profiling of human oocytes following in vivo or in vitro maturation. Hum. Reprod. 23, 1138-1144.
    Krueger, F., Andrews, S.R., 2011. Bismark: a flexible aligner and methylation caller for Bisulfite-Seq applications. Bioinformatics 27, 1571-1572.
    Kuhtz, J., Romero, S., De Vos, M., Smitz, J., Haaf, T., Anckaert, E., 2014. Human in vitro oocyte maturation is not associated with increased imprinting error rates at LIT1, SNRPN, PEG3 and GTL2. Hum. Reprod. 29, 1995-2005.
    Kuleshov, M.V., Jones, M.R., Rouillard, A.D., Fernandez, N.F., Duan, Q., Wang, Z., Koplev, S., Jenkins, S.L., Jagodnik, K.M., Lachmann, A., 2016. Enrichr: a comprehensive gene set enrichment analysis web server 2016 update. Nucl. Acids Res. 44, 90-97.
    Lee, Y.S., Latham, K.E., Vandevoort, C.A., 2008. Effects of in vitro maturation on gene expression in rhesus monkey oocytes. Physiol. Genomics 35, 145-158.
    Li, J., Chen, J., Sun, T., Zhang, S., Jiao, T., Chian, R.C., Li, Y., Xu, Y., 2021. Chromosome aneuploidy analysis in embryos derived from in vivo and in vitro matured human oocytes. J. Transl. Med. 19, 416.
    Li, Y., Zhang, Z., Chen, J., Liu, W., Lai, W., Liu, B., Li, X., Liu, L., Xu, S., Dong, Q., et al., 2018. Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature 564, 136-140.
    Lim, J.H., Yang, S.H., Chian, R.C., 2007. New alternative to infertility treatment for women without ovarian stimulation. Reprod. Biomed. Online 14, 547-549.
    Liu, Y., Tao, W., Wu, S., Zhang, Y., Nie, H., Hou, Z., Zhang, J., Yang, Z., Chen, Z.-J., Wang, J., et al., 2024. Maternal mRNA deadenylation is defective in in vitro matured mouse and human oocytes. Nat. Commun. 15, 5550.
    Lucifero, D., Mann, M.R.W., Bartolomei, M.S., Trasler, J.M., 2004. Gene-specific timing and epigenetic memory in oocyte imprinting. Hum. Mol. Genet. 13, 839-849.
    Martin, M., 2011. Cutadapt removes adapter sequences from high-throughput sequencing reads. EMBnet J. 17, 10-12.
    Miranda, A.G., Seneda, M.M., Faustino, L.R., 2023. DNA methylation associated with polycystic ovary syndrome: a systematic review. Arch. Gynecol. Obstet. 309 (2), 373–383.
    Morato, A.L.C., Verruma, C.G., Furtado, C.L.M., Dos Reis, R.M., 2024. In vitro maturation of oocytes: what is already known? Biol. Reprod. 112, 18-30.
    Pliushch, G., Schneider, E., Schneider, T., El Hajj, N., Rosner, S., Strowitzki, T., Haaf, T., 2015. In vitro maturation of oocytes is not associated with altered deoxyribonucleic acid methylation patterns in children from in vitro fertilization or intracytoplasmic sperm injection. Fertil. Steril. 103, 720-727.
    Saucedo-Cuevas, L., Ma, M.P.Q., Le, A.H., Akin, N., Pham, T.D., Ho, T.M., Pita, G., Gonzalez-Neira, A., De Vos, M., et al., 2024. Epigenetic variation in neonatal tissues in infants conceived using capacitation-in vitro maturation vs. in vitro fertilization. Fertil. Steri. 121, 506-518.
    Shirane, K., Toh, H., Kobayashi, H., Miura, F., Chiba, H., Ito, T., Kono, T., Sasaki, H., 2013. Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases. PLoS Genet. 9 (4), e1003439.
    Song, X.L., Lu, C.L., Zheng, X.Y., Nisenblat, V., Zhen, X.M., Yang, R., Li, M., Li, R., Yuan, Y.F., Ma, C.H., et al., 2020. Enhancing the scope of in vitro maturation for fertility preservation: transvaginal retrieval of immature oocytes during endoscopic gynaecological procedures. Hum. Reprod. 35, 837-846.
    Spits, C., Guzman, L., Mertzanidou, A., Jacobs, K., Ortega-Hrepich, C., Gilchrist, R.B., Thompson, J.G., De Vos, M., Smitz, J., Sermon, K., 2014. Chromosome constitution of human embryos generated after in vitro maturation including 3-isobutyl-1-methylxanthine in the oocyte collection medium. Hum. Reprod. 30, 653-663.
    Stewart, K.R., Veselovska, L., Kelsey, G., 2016. Establishment and Functions of DNA Methylation in the Germline. Epigenomics 8, 1399-1413.
    Takeuchi, H., Yamamoto, M., Fukui, M., Inoue, A., Maezawa, T., Nishioka, M., Kondo, E., Ikeda, T., Matsumoto, K., Miyamoto, K., 2022. Single-cell profiling of transcriptomic changes during in vitro maturation of human oocytes. Reprod. Med. Biol. 21, e12464.
    Virant-Klun, I., Bauer, C., Stahlberg, A., Kubista, M., Skutella, T., 2018. Human oocyte maturation in vitro is improved by co-culture with cumulus cells from mature oocytes. Reprod. Biomed. Online 36, 508-523.
    Walls, M.L., Hunter, T., Ryan, J.P., Keelan, J.A., Nathan, E., Hart, R.J., 2015. In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes. Hum. Reprod. 30, 88-96.
    Wood, J.R., Dumesic, D.A., Abbott, D.H., Strauss, J.F., 3rd, 2007. Molecular abnormalities in oocytes from women with polycystic ovary syndrome revealed by microarray analysis. J. Clin. Endocrinol. Metab. 92, 705-713.
    Yang, S.H., Patrizio, P., Yoon, S.H., Lim, J.H., Chian, R.C., 2012. Comparison of pregnancy outcomes in natural cycle IVF/M treatment with or without mature oocytes retrieved at time of egg collection. Syst Biol. Reprod. Med. 58, 154-159.
    Chian, R.-C., Kee, K., Xie, W., Wang, L., Zhou, J.-H., Xie, Q.-G., Xing, Y.-X., Zhang, Y., Yang, Z.-Y., Ye, M., 2020. Single-cell multiomic analysis of in vivo and in vitro matured human oocytes. Human Reproduction 35, 886-900.
    Yoshida, H., Abe, H., Arima, T., 2013. Quality evaluation of IVM embryo and imprinting genes of IVM babies. J. Assist Reprod. Genet. 30, 221-225.
    Yu, G., Wang, L.-G., He, Q.-Y., 2015. ChIPseeker: an R/Bioconductor package for ChIP peak annotation, comparison and visualization. Bioinformatics 31, 2382-2383.
    Zhao, H., Li, T., Zhao, Y., Tan, T., Liu, C., Liu, Y., Chang, L., Huang, N., Li, C., Fan, Y., et al., 2019. Single-cell transcriptomics of human oocytes: environment-driven metabolic competition and compensatory mechanisms during oocyte maturation. Antioxid. Redox Signal. 30, 542-559.
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  • 收稿日期:  2025-03-04
  • 录用日期:  2025-05-06
  • 修回日期:  2025-04-30
  • 刊出日期:  2026-01-31

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