- RNA-Seq transcriptome reveals different molecular responses during human and mouse oocyte maturation and fertilization. - The objective of this study is to elucidate the different molecular mechanisms underlying oocyte maturation and fertilization between human and mouse.. - Results: A comparative transcriptome analysis was performed to identify the differentially expressed genes and associated biological processes between human and mouse oocytes. - In total, 8513 common genes, as well as 15, 165 and 6126 uniquely expressed genes were detected in human and mouse MII oocytes, respectively. - Additionally, the ratios of non-homologous genes in human and mouse MII oocytes were 37 and 8%, respectively. - Conclusions: This study demonstrates that human and mouse oocytes exhibit significant differences in gene expression profiles during oocyte maturation, which probably deciphers the differential molecular responses to oocyte maturation and fertilization. - The significant differences between human and mouse oocytes limit the generalizations from mouse to human oocyte maturation. - Knowledge about the limitations of animal models is crucial when exploring a complex process such as human oocyte maturation and fertilization.. - The necessary transcripts deposited in fully-grown GV oocytes are produced during the period of oocyte growth, which is essential for oocyte maturation and fertilization [12]. - Also, the selective degradation of tran- scripts that occurs during oocyte maturation is required for meiotic maturation and oocyte-to-embryo transition [13–15]. - Although human and mouse oocytes undergo degradation of maternal mRNAs during oocyte matur- ation, the time period of oocyte to embryo transition is different between human and mouse.. - Several studies have compared the microarray data [16–18], however the differences in oocyte maturation and fertilization between human and mouse have not been fully characterized. - Here, we compared the RNA- Seq data of human and mouse oocytes during the transi- tion from the GV stage to the MII stage. - Moreover, the ratio of non- homologous genes is significantly different between hu- man and mouse oocytes. - Slight differences in molecular features between mouse GV and MII oocytes. - Differences in gene expression profiles between mouse GV and MII oocytes were analyzed to determine the sig- nificantly changed transcripts that may contribute to meiotic maturation and fertilization processes. - In the present study, the number of genes that are uniquely expressed in mouse GV and MII oocytes were 2243 and 430, respectively (Additional files 1 and 2). - Of particular note, 430 transcripts appeared to be expressed uniquely in MII oocytes.. - To ascertain differences in gene expression profiles between GV and MII oocytes, we used Clusterprofiler R package to analyze gene ontology of genes that are exclusively expressed in GV and MII oocytes [19]. - shown in Additional files 3 and 4, of the 335 biological processes (BP), 239 are significantly correlated with the transcripts that are degraded during the GV to MII tran- sition, whereas 96 are closely associated with the tran- scripts that appeared in MII oocytes. - may be differentially regulated in GV oocytes and MII oocytes. - The GO terms indicate that newly appearing genes in MII oocytes may play an important role in oocyte maturation and fertilization.. - 1 The difference in gene expression patterns between mouse GV and MII oocytes. - c: The enriched GO categories of differentially expressed genes in human MII oocytes. - d: The expression level of Tnni3 in GV and MII oocytes. - Collectively, these data suggest that the genes that are exclusively expressed in MII oocytes may play important roles in fertilization.. - Significant differences in molecular features between human GV and MII oocytes. - To explore the molecular mechanisms in human oocyte maturation, we compared the gene expression profiles between human GV and MII oocytes. - The numbers of genes that were exclusively expressed in human GV and MII oocytes were 2488 and 3790, respectively (Additional files 5 and 6). - contrast to mouse MII oocytes, there were 3790 tran- scripts exclusively expressed in MII oocytes.. - To further determine the features of human GV and MII oocytes, we performed GO and KEGG analysis of the genes that are uniquely expressed in human GV and MII oocytes. - complete degradation of GADD45G during the GV-to-MII transition suggests its role in oocyte maturation (Fig. - Comparison of gene expression profiles between human and mouse oocytes. - Oogenesis is a species specialized developmental process and the mouse is not the most suitable animal model for humans, especially when exploring oocyte maturation and fertilization [30, 31]. - To examine the differences in regulating oocyte maturation, we compared the gene ex- pression profiles between human and mouse oocytes. - A total of 9365 genes overlapped between human and mouse GV oocytes (Fig. - transcripts specifically expressed in the GV oocytes over- lapped in human and mouse (Fig. - Furthermore, 8513 genes overlapped between human MII and mouse MII oocytes (Fig. - 4c), of which only 19 transcripts that specially were expressed in MII oocytes overlapped in human and mouse (Fig. - Collectively, these data sug- gest that there is a different regulatory network respon- sible for human and mouse oocyte maturation.. - The ratio of non-homologous genes in human and mouse MII oocytes. - The ratio of non-homologous genes in oocytes could pinpoint the differences among species. - 3 The different gene expression patterns in human GV and MII oocytes. - a: Overlap of differentially expressed genes between human GV and MII oocytes. - c: The enriched signaling pathways of differentially expressed genes in human GV oocytes. - d: The enriched GO terms within differentially expressed genes unique to the human MII oocytes. - The enriched signaling pathways of differentially expressed genes in human MII oocytes. - f: The expression level of GADD45G in GV and MII oocytes. - expressed genes would discriminate the species-specific molecular pathways between human and mouse oocyte maturation. - To further determine the ratio of non- homologous genes in human and mouse MII oocytes, we downloaded the homologous gene database from NCBI (ftp://ftp.ncbi.nih.gov/pub/HomoloGene. - Whereas 1183 genes are non-homologous genes in mouse MII oocytes, and the ratio of non-homologous genes is 8% (Fig. - To further explore the functions of non-homologous genes, we performed GO analysis on non-homologous genes in human and mouse MII oocytes. - are also enriched in human MII oocytes (Add- itional file 13). - However, we did not acquire the GO terms of non-homologous genes in mouse MII oocytes (data not shown). - These results indicate that there is a significant difference between human and mouse MII oocytes.. - Al- though mouse is suited for studies of oocyte maturation and fertilization, the differences between mouse and human also need to be focused. - Comparative analysis of RNA-Seq data has provided informative insights into the differences between human and mouse oocytes.. - Oocyte maturation and fertilization have been ex- plored for many years . - however, little is known regarding the different mechanisms between hu- man and mouse. - Here, we analyzed the transcriptomes of human and mouse GV and MII oocytes to explore the differences between human and mouse oocytes at the transcriptional level [22, 35]. - As reported above, the regulation of oocyte maturation and fertilization exhibits different features in human and mouse oocytes. - For ex- ample, compared to GV oocytes, the number of appar- ent transcripts in mouse and human MII oocytes are 430 and 3790, respectively (Figs. - Add- itionally, differential gene expression analysis between human and mouse oocytes identified numerous signifi- cant differentially expressed genes that were enriched for typical or species-specific pathways and biological pro- cesses. - The transcriptomes of human and mouse oocytes are highly variable, and the human oocytes exhibit more complexity than mouse oocytes.. - For ex- ample, BTG4, CNOT6L and ZAR1/2 participate in the destruction of target specific transcripts during oocyte maturation . - However, the differences of se- lectively degraded transcripts between human and mouse have not been explored in detail. - Therefore, the difference in select- ively degraded transcripts between human and mouse oocytes suggests deviations of regulatory mechanisms that control oocyte maturation.. - On the other hand, there are certain transcripts that appear to be up-regulated in MII oocytes. - Therefore, the transcripts that exclusively appeared in MII oocytes may not be newly transcribed. - Two-level analysis of transcriptome demonstrated that the significant differences in molecular responses exist between human and mouse oocytes. - The ratio of non-homologous genes in human MII oocytes is four times higher than that in mouse MII oo- cytes. - However, most GO categories of non-homologous genes in human MII oocytes are conserved biological processes including “adenylate cyclase-activating G protein- coupled receptor signaling pathway” and “cAMP-mediated signaling”. - Unexpectedly, we hardly detected any GO terms in non-homologous genes of mouse MII oocytes. - Therefore, it shows potential shortcomings related to the use of mouse model to explore the oocyte maturation process in human.. - In summary, human and mouse oocytes exhibit diver- gent transcriptomes at the fully-grown GV and MII stages, probably deciphering the differential molecular response to oocyte maturation and fertilization. - Critical factors involved in oocyte maturation were found to be differentially expressed between human and mouse oo- cytes. - Moreover, human MII oocytes exhibited a higher ratio of non-homologous genes compared to mouse MII oocytes, which were enriched for various biological. - 4 The different gene expression patterns between human and mouse oocytes. - a: Venn diagram shows overlapping of differentially expressed genes in human and mouse GV oocytes. - b: Overlap of differentially expressed genes between human GV-specific genes and mouse GV-specific genes. - c: Venn diagram shows overlapping of differentially expressed genes in human and mouse MII oocytes. - d: Overlap of differentially expressed genes between human MII-specific genes and mouse MII-specific genes. - These findings show significant differences in gene expression profiles between human and mouse oocytes, limiting the generalizations from mouse to hu- man oocyte maturation. - Knowledge about the limita- tions of animal models is crucial when exploring a complex process such as human oocyte maturation and fertilization.. - 5 The difference of non-homologous genes between human and mouse MII oocytes. - b: The ratio of non-homologous genes in human MII oocytes. - Venn diagram shows overlapping genes in mouse homologous genes database and mouse MII expressed genes. - d: The ratio of non- homologous genes in mouse MII oocytes. - e: The enriched biological processes within non-homologous genes unique to the human MII oocytes. - Normalized FPKM and RPKM values for mouse and human oocyte maturation and fertilization stages were ob- tained from GEO database (GSE71434_FPKM_stage.txt.gz;. - 30 years) GV and MII oocytes from Reyes et al.. - pub/HomoloGene/) to calculate the ratios of the non- homologous genes in mouse and human MII oocytes.. - GO categories of mouse MII oocyte-specific expressed genes.. - GO categories of human GV oocyte-specific expressed genes.. - KEGG categories of human GV oocyte-specific expressed genes.. - GO categories of human MII oocyte-specific expressed genes.. - KEGG categories of human MII oocyte-specific expressed genes.. - Human MII oocyte non-homologous gene list.. - Mouse MII oocyte non-homologous gene list.. - GO categories of human MII oocyte non- homologous genes.
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