Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed human metaphase II oocytes

doi:10.1007/s11684-020-0792-7

Front. Med.

2021, Vol. 15

Issue (1) : 144-154 https://doi.org/10.1007/s11684-020-0792-7

RESEARCH ARTICLE

Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed human metaphase II oocytes

Ying Huo^1,^2,^3,⁴, Peng Yuan^1,^3,⁴, Qingyuan Qin^1,^3,⁴, Zhiqiang Yan^1,^3,^4,⁵, Liying Yan^1,^3,^4,⁶, Ping Liu^1,^3,⁴, Rong Li^1,^3,^4,⁶, Jie Yan^1,^3,⁴(

), Jie Qiao^1,^3,^4,^5,⁶

¹. Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing 100191, China
². Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University, Beijing 100191, China
³. Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproduction, Beijing 100191, China
⁴. Key Laboratory of Assisted Reproduction, Ministry of Education, Beijing 100191, China
⁵. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China
⁶. National Clinical Research Center of Obstetrics and Gynecology, Beijing 100191, China

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Abstract

Oocyte cryopreservation is widely used for clinical and social reasons. Previous studies have demonstrated that conventional slow-freezing cryopreservation procedures, but not storage time, can alter the gene expression profiles of frozen oocytes. Whether vitrification procedures and the related frozen storage durations have any effects on the transcriptomes of human metaphase II oocytes remain unknown. Four women (30–32 years old) who had undergone IVF treatment were recruited for this study. RNA-Seq profiles of 3 fresh oocytes and 13 surviving vitrified-thawed oocytes (3, 3, 4, and 3 oocytes were cryostored for 1, 2, 3, and 12 months) were analyzed at a single-cell resolution. A total of 1987 genes were differentially expressed in the 13 vitrified-thawed oocytes. However, no differentially expressed genes were found between any two groups among the 1-, 2-, 3-, and 12-month storage groups. Further analysis revealed that the aberrant genes in the vitrified oocytes were closely related to oogenesis and development. Our findings indicated that the effects of vitrification on the transcriptomes of mature human oocytes are induced by the procedure itself, suggesting that long-term cryostorage of human oocytes is safe.

Keywords human metaphase II oocyte vitrification cryostorage duration single-cell RNA-Seq lncRNA

Corresponding Author(s): Jie Yan

Just Accepted Date: 10 July 2020 Online First Date: 01 September 2020 Issue Date: 11 February 2021

Cite this article:

Ying Huo,Peng Yuan,Qingyuan Qin, et al. Effects of vitrification and cryostorage duration on single-cell RNA-Seq profiling of vitrified-thawed human metaphase II oocytes[J]. Front. Med., 2021, 15(1): 144-154.

URL:

https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0792-7
https://academic.hep.com.cn/fmd/EN/Y2021/V15/I1/144

Fig.1 Quality control of the RNA-Seq data and pairwise comparisons between cryopreserved groups. (A) PCA of the transcriptomes of single human oocytes. Oocytes with the same cryostorage duration are indicated with symbols of the same shape. PC1 and PC2 represent the top two dimensions of the genes showing differential expression among these oocytes. (B) Relative median TIN of single human oocytes. The median TIN of each single cell was divided by the average median TIN of fresh MII oocytes. (C) Pairwise comparisons between two groups among the 1-, 2-, 3-, and 12-month cryostorage groups.

Fig.2 Differentially expressed genes between fresh and cryopreserved human MII oocytes. (A) Heatmap of the differentially expressed genes between fresh and cryopreserved oocytes. The expression level of each gene was normalized using the Z-score. (B) Enriched GO terms of the downregulated genes in cryopreserved oocytes. (C) Enriched GO terms of the upregulated genes in cryopreserved oocytes. (D) Enriched KEGG pathways of the downregulated genes in cryopreserved oocytes. (E) Enriched KEGG pathways of the upregulated genes in cryopreserved oocytes.

Fig.3 Differentially expressed genes between fresh oocytes and cryopreserved oocytes in four groups. (A) Scatter plot of the average gene expression between fresh and cryopreserved oocytes. Downregulated genes in cryopreserved oocytes are shown in red, upregulated genes are depicted in green, and stably expressed genes are presented in black. (B) Venn diagram of the common downregulated genes in the four cryopreserved groups in comparison with the fresh group. (C) Venn diagram of the common upregulated genes in the four cryopreserved groups in comparison with the fresh group. (D) Enriched GO terms of the 52 common downregulated genes among the four cryopreserved groups.

Fig.4 Expression patterns of lncRNAs among fresh and cryopreserved human MII oocytes. (A) Unsupervised hierarchical clustering of the lncRNA expression profiles of 16 samples. (B) Heatmap of the differentially expressed lncRNAs between fresh and cryopreserved oocytes. Z-scores with colors from blue to red indicate the expression levels from low to high. (C) Scatter plot of lncRNA expression between the fresh oocyte group and the 1-, 2-, 3-, and 12-month cryopreserved groups. (D) Venn diagram of the commonly downregulated lncRNAs in the four cryopreserved groups in comparison with the control group. (E) Scatter plot of the average gene expression between two groups among the 1-, 2-, 3-, and 12-month groups.

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