Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility

Bhat, Muzaffer Ahmed; Sharma, Jai Bhagwan; Roy, Kallol Kumar; Sengupta, Jayasree; Ghosh, Debabrata

doi:10.1186/s12958-019-0465-z

Cited by 34 publications

(23 citation statements)

References 51 publications

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“…These include a set of 10 genes, such as EIF1AY, DDX3Y, ZFY, TTTY14 and NLGN4Y. Mutations in and differential expression of these Y-chromosome genes, such as the DDXY3 gene, have been linked with male infertility and reduction of germ cell numbers [ 31 , 32 ], which are age related processes, also in other tissues such as sperm [ 33 ]. Our finding of age-correlated CpGs existing in the rest of the Y-genes likely has an underlying biological reason, which should be investigated in future studies.…”

Section: Resultsmentioning

confidence: 99%

Male-specific age estimation based on Y-chromosomal DNA methylation

Vidaki

González

Jiménez

et al. 2021

Aging

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Although DNA methylation variation of autosomal CpGs provides robust age predictive biomarkers, no male-specific age predictor exists based on Y-CpGs yet. Since sex chromosomes play an important role in aging, a Y-chromosome-based age predictor would allow studying male-specific aging effects and would also be useful in forensics. Here, we used blood-based DNA methylation microarray data of 1,057 males from six cohorts aged 15-87 and identified 75 Y-CpGs with an interquartile range of ≥0.1. Of these, 22 and six were significantly hyper- and hypomethylated with age (p(cor)<0.05, Bonferroni), respectively. Amongst several machine learning algorithms, a model based on support vector machines with radial kernel performed best in male-specific age prediction. We achieved a mean absolute deviation (MAD) between true and predicted age of 7.54 years (cor=0.81, validation) when using all 75 Y-CpGs, and a MAD of 8.46 years (cor=0.73, validation) based on the most predictive 19 Y-CpGs. The accuracies of both age predictors did not worsen with increased age, in contrast to autosomal CpG-based age predictors that are known to predict age with reduced accuracy in the elderly. Overall, we introduce the first-of-its-kind male-specific epigenetic age predictor for future applications in aging research and forensics.

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Section: Resultsmentioning

confidence: 99%

Male-specific age estimation based on Y-chromosomal DNA methylation

Vidaki

González

Jiménez

et al. 2021

Aging

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“…The datasets were combined and processed by the sva package to remove batch effects because the datasets came from multiple cohorts and array platforms (20) and then were normalized by the limma package before further analysis (21). GSE120103 contains 36 endometrial samples of fertile or infertile women with or without endometriosis (22), which were downloaded and processed by the GEOquery package. The raw data are available in NCBI-GEO, from which they can be downloaded and analysed.…”

Section: Data Collection and Processingmentioning

confidence: 99%

Identification and Validation of the Signatures of Infiltrating Immune Cells in the Eutopic Endometrium Endometria of Women With Endometriosis

Chen

Zhou

et al. 2021

Front. Immunol.

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Endometriosis is an oestrogen-dependent chronic inflammatory process with primary symptoms including dysmenorrhea, chronic pelvic pain, and infertility. The immune environment of the endometrium is essential for successful embryo implantation and ongoing pregnancy. In this study, we assessed the composition, density, and distribution of infiltrating immune cells in the endometria of women with endometriosis. Gene expression profiles of endometrial samples were downloaded from the Gene Expression Omnibus (GEO) database. We found that the TNF signalling pathway, the IL-17 signalling pathway, and the MAPK signalling pathway were significantly enriched in the eutopic endometria of women with endometriosis. The fractions and proportion of infiltrating immune cells were estimated by the CIBERSORT, MCP-counter, and ImmuCellAI methods. We found that the proportions of CD8+ T cells, activated NK cells, and follicular helper T cells were significantly higher in the endometria of women with endometriosis than in the endometria of normal controls, while the proportions of M2 macrophages and resting mast cells were significantly lower in the eutopic endometria. In GSE120103 (n = 36), we found that elevated CD8+ T cells in endometriosis increased the risk of infertility (P = 0.0019). The area under the receiver operating characteristic (ROC) curve (AUC) of CD8+ T cells to distinguish fertile and infertile endometriosis was 0.914. In clinical samples (n = 40), we found that the proportions of CD8+ T cells and CD56+ NK cells were significantly higher in the eutopic endometria of women with endometriosis than in the endometria of normal controls, while the proportion of CD163+ macrophages were lower in the eutopic endometria. The AUCs of CD8+ T cells and CD163+ macrophages were 0.727 and 0.833, respectively, which indicated that CD8 and CD163 were potential diagnostic markers for endometriosis. In conclusion, our results demonstrated that increased CD8+ T cells and CD56+ NK cells and decreased CD163+ macrophages within the eutopic endometria of women with endometriosis reveal a proinflammatory feature in the endometrial immune environment and that elevated CD8+ T cells increase the risk of infertility in women with the disease.

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“…Other genes include RPS27, found by Floristan et al . (2020 ) to have bimodal expression in several tumor types, and USP9AY, found to show bimodality in endometrium ( Bhat et al, 2019 ). Interestingly, among the 46 genes with bimodality in more than one tumor type, 12 are mapped to the Y chromosome (p<10 -5 ), an unexpected observation due to the low gene density in this chromosome.…”

Section: Discussionmentioning

confidence: 99%

An integrated approach to identify bimodal genes associated with prognosis in câncer

et al. 2021

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Bimodal gene expression (where a gene expression distribution has two maxima) is associated with phenotypic diversity in different biological systems. A critical issue, thus, is the integration of expression and phenotype data to identify genuine associations. Here, we developed tools that allow both: i) the identification of genes with bimodal gene expression and ii) their association with prognosis in cancer patients from The Cancer Genome Atlas (TCGA). Bimodality was observed for 554 genes in expression data from 25 tumor types. Furthermore, 96 of these genes presented different prognosis when patients belonging to the two expression peaks were compared. The software to execute the method and the corresponding documentation are available at the Data access section.

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Genomic evidence of Y chromosome microchimerism in the endometrium during endometriosis and in cases of infertility

Cited by 34 publications

References 51 publications

Male-specific age estimation based on Y-chromosomal DNA methylation

Male-specific age estimation based on Y-chromosomal DNA methylation

Identification and Validation of the Signatures of Infiltrating Immune Cells in the Eutopic Endometrium Endometria of Women With Endometriosis

An integrated approach to identify bimodal genes associated with prognosis in câncer

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