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Single-cell Analysis of Differences in Transcriptomic Profiles of Oocytes and Cumulus Cells at GV, MI, MII Stages From PCOS Patients

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Single-cell Analysis of Differences in Transcriptomic Profiles of Oocytes and Cumulus Cells at GV, MI, MII Stages From PCOS Patients

Qiwei Liu et al. Sci Rep.

Abstract

Polycystic ovary syndrome (PCOS) is a common frequent endocrine disorder among women of reproductive age. Although assisted reproductive techniques (ARTs) are used to address subfertility in PCOS women, their effectiveness is not clear. Our aim was to compare transcriptomic profiles of oocytes and cumulus cells (CCs) between women with and without PCOS, and assess the effectiveness of ARTs in treating PCOS patients. We collected oocytes and CCs from 16 patients with and without PCOS patients to categorize them into 6 groups according to oocyte nuclear maturation. Transcriptional gene expression of oocyte and CCs was determined via single-cell RNA sequencing. The ratio of fertilization and cleavage was higher in PCOS patients than in non-PCOS patients undergoing ARTs, and there was no difference in the number of high-quality embryos between the groups. Differentially expressed genes including PPP2R1A, PDGFRA, EGFR, GJA1, PTGS2, TNFAIP6, TGF-β1, CAV1, INHBB et al. were investigated as potential causes of PCOS oocytes and CCs disorder at early stages, but their expression returned to the normal level at the metaphase II (MII) stage via ARTs. In conclusion, ARTs can improve the quality of cumulus-oocyte complex (COC) and increase the ratio of fertilization and cleavage in PCOS women.

Figures

Figure 1
Figure 1. Heatmap of differentially expressed genes in oocytes with and without PCOS at GV, MI, MII stage.
Green corresponds to up-expressed genes; red corresponds to down-expressed genes. NO-GV, oocyte at GV stage from normal women; PO-GV, oocyte at GV stage from women with PCOS; NO-MI, oocyte at MI stage from normal women; PO-MI, oocyte at MI stage from women with PCOS; NO-MII, oocyte at MII stage from normal women; PO-MII, oocyte at MII stage from women with PCOS.
Figure 2
Figure 2. Heatmap of differentially expressed genes in CCs with and without PCOS at GV, MI, MII stage.
Green corresponds to up-expressed genes; red corresponds to down-expressed genes. CCs, cumulus cells. NC-GV, CCs at GV stage from normal women; PC-GV, CCs at GV stage from women with PCOS; NC-MI, CCs at MI stage from normal women; PC-MI, CCs at MI stage from women with PCOS; NC-MII, CCs at MII stage from normal women; PC-MII, CCs at MII stage from women with PCOS.
Figure 3
Figure 3. Significantly signaling pathway involved differentially expressed genes.
The threshold of Padj was set at < 0.05 to find significantly signaling pathway. The listed genes are the differentially expressed genes analyzed in our study in each pathway. (A) Significantly signaling pathway of oocytes comparing PCOS patients with non-PCOS patients. (B) Significantly signaling pathway of CCs comparing PCOS patients with non-PCOS patients.
Figure 4
Figure 4. Heatmap of the expression patterns of selected genes at different stages.
(A) Heatmap of expression patterns of selected genes in oocyte groups. (B) Heatmap of expression patterns of selected genes in CCs groups.
Figure 5
Figure 5. Differentially expressed genes in PCOS oocyte studied through single-cell RNA sequencing.
The threshold of Padj was set at < 0.05 to find significantly expressed genes. (A) Boxplot showing differentially expressed genes involved in meiosis process. (B) Boxplot showing differentially expressed genes included in gap junction pathway. (C) Boxplot showing differentially expressed genes related to hormone receptor signaling. (D) Boxplot showing differentially expressed genes involved in DNA repairing. (E) Boxplot showing significantly expressed genes are related to secreted factors. *Padj < 0.05. The y axis indicates the log2 (FPKM + 1) expression levels.
Figure 6
Figure 6. Differentially expressed genes in PCOS CCs studied through single-cell RNA sequencing.
The threshold of Padj was set at < 0.05 to find significantly expressed genes. (A) Boxplot showing differentially expressed genes involved in CCs expansion. (B) Boxplot showing differentially expressed genes related to hormone receptor signaling. (C) Boxplot showing differentially expressed genes included in folliculogenesis. (D) Boxplot showing differentially expressed genes involved in gap junction. (E) Boxplot showing significantly expressed genes related to oxidative stress and genes predicting quality of oocyte. *Padj < 0.05. The y axis indicates the log2 (FPKM + 1) expression levels.

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