Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization
Problem DNA methylation profile in mid‐secretory phase of endometrium is reported to be varied from other phases in natural menstrual cycle. Therefore, we intended to study the impairment in endometrial receptivity by performing whole‐genome methylation and gene expression profiling in endometrium o...
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| Veröffentlicht in: | American journal of reproductive immunology (1989) 2020-01, Vol.83 (1), p.e13196-n/a |
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| container_title | American journal of reproductive immunology (1989) |
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| creator | Pathare, Amruta D. S. Hinduja, Indira |
| description | Problem
DNA methylation profile in mid‐secretory phase of endometrium is reported to be varied from other phases in natural menstrual cycle. Therefore, we intended to study the impairment in endometrial receptivity by performing whole‐genome methylation and gene expression profiling in endometrium of recurrent implantation failure patients (RIF) during IVF under controlled ovarian stimulation (COS).
Method of study
Endometrial biopsies were collected from IVF‐RIF patients (cases, n = 6) and healthy fertile oocyte donors (controls, n = 6) undergoing COS after 6/7th day of human chorionic gonadotropin administration. The whole‐genome methylation and gene expression microarray were performed and analysed by GenomeStudio software (P |
| doi_str_mv | 10.1111/aji.13196 |
| format | Article |
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DNA methylation profile in mid‐secretory phase of endometrium is reported to be varied from other phases in natural menstrual cycle. Therefore, we intended to study the impairment in endometrial receptivity by performing whole‐genome methylation and gene expression profiling in endometrium of recurrent implantation failure patients (RIF) during IVF under controlled ovarian stimulation (COS).
Method of study
Endometrial biopsies were collected from IVF‐RIF patients (cases, n = 6) and healthy fertile oocyte donors (controls, n = 6) undergoing COS after 6/7th day of human chorionic gonadotropin administration. The whole‐genome methylation and gene expression microarray were performed and analysed by GenomeStudio software (P < .05 by Illumina Custom Model), whereas the enrichment analysis was performed using “Database for Annotation, Visualization and Integrated Discovery” (DAVID, V6.8). Significant differentially methylated genes were correlated with dys‐regulated genes using Pearson's correlation.
Results
Differential methylation in RIF patients revealed 448 CpG sites. The enrichment analysis showed aberrant methylation in genes involved in immunological response and G protein activity. Methylation in NLRP2 gene in inflammatory pathway had significant negative correlation with gene expression (P = .008), whereas SERPINA5 gene that is already known to be involved in endometrial receptivity was observed to be hypomethylated in promoter region with highest delta beta value and up‐regulated in gene expression analysis.
Conclusion
The aberrant methylation of genes involved in immunological functions and G protein activation was found to be prevalent which might suggest a role in endometrial receptivity. However, the findings need to be further validated on a larger cohort of IVF‐RIF patients.</description><identifier>ISSN: 1046-7408</identifier><identifier>EISSN: 1600-0897</identifier><identifier>DOI: 10.1111/aji.13196</identifier><identifier>PMID: 31595580</identifier><language>eng</language><publisher>Denmark: Wiley Subscription Services, Inc</publisher><subject>Chorionic gonadotropin ; controlled ovarian stimulation ; CpG islands ; Deoxyribonucleic acid ; DNA ; DNA fingerprinting ; DNA methylation ; DNA microarrays ; Endometrium ; fertilization in vitro ; Gene expression ; gene expression profiling ; Genomes ; Gonadotropins ; Immune response ; Immunology ; In vitro fertilization ; Inflammation ; Menstrual cycle ; Pituitary (anterior)</subject><ispartof>American journal of reproductive immunology (1989), 2020-01, Vol.83 (1), p.e13196-n/a</ispartof><rights>2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><rights>2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.</rights><rights>Copyright © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3536-9d61d459377938c956186e4b3cab60d5658c49230d1a5319034a3cecfb75c46d3</citedby><cites>FETCH-LOGICAL-c3536-9d61d459377938c956186e4b3cab60d5658c49230d1a5319034a3cecfb75c46d3</cites><orcidid>0000-0002-5608-2370</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Faji.13196$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Faji.13196$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,777,781,1412,27905,27906,45555,45556</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31595580$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pathare, Amruta D. S.</creatorcontrib><creatorcontrib>Hinduja, Indira</creatorcontrib><title>Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization</title><title>American journal of reproductive immunology (1989)</title><addtitle>Am J Reprod Immunol</addtitle><description>Problem
DNA methylation profile in mid‐secretory phase of endometrium is reported to be varied from other phases in natural menstrual cycle. Therefore, we intended to study the impairment in endometrial receptivity by performing whole‐genome methylation and gene expression profiling in endometrium of recurrent implantation failure patients (RIF) during IVF under controlled ovarian stimulation (COS).
Method of study
Endometrial biopsies were collected from IVF‐RIF patients (cases, n = 6) and healthy fertile oocyte donors (controls, n = 6) undergoing COS after 6/7th day of human chorionic gonadotropin administration. The whole‐genome methylation and gene expression microarray were performed and analysed by GenomeStudio software (P < .05 by Illumina Custom Model), whereas the enrichment analysis was performed using “Database for Annotation, Visualization and Integrated Discovery” (DAVID, V6.8). Significant differentially methylated genes were correlated with dys‐regulated genes using Pearson's correlation.
Results
Differential methylation in RIF patients revealed 448 CpG sites. The enrichment analysis showed aberrant methylation in genes involved in immunological response and G protein activity. Methylation in NLRP2 gene in inflammatory pathway had significant negative correlation with gene expression (P = .008), whereas SERPINA5 gene that is already known to be involved in endometrial receptivity was observed to be hypomethylated in promoter region with highest delta beta value and up‐regulated in gene expression analysis.
Conclusion
The aberrant methylation of genes involved in immunological functions and G protein activation was found to be prevalent which might suggest a role in endometrial receptivity. However, the findings need to be further validated on a larger cohort of IVF‐RIF patients.</description><subject>Chorionic gonadotropin</subject><subject>controlled ovarian stimulation</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA fingerprinting</subject><subject>DNA methylation</subject><subject>DNA microarrays</subject><subject>Endometrium</subject><subject>fertilization in vitro</subject><subject>Gene expression</subject><subject>gene expression profiling</subject><subject>Genomes</subject><subject>Gonadotropins</subject><subject>Immune response</subject><subject>Immunology</subject><subject>In vitro fertilization</subject><subject>Inflammation</subject><subject>Menstrual cycle</subject><subject>Pituitary (anterior)</subject><issn>1046-7408</issn><issn>1600-0897</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp1kctOxSAQQInR-F74A4bEjS6qcCm0Xd74NkY3um4onSo3fQlUc_0P_9epVRcmsoGBM4eBIWSPs2OO40Qv7DEXPFMrZJMrxiKWZskqrlmsoiRm6QbZ8n7BGO6LZJ1sCC4zKVO2ST7mBTin20DP7ua0gfC8rHWwXUt711W2tu0T1VUFJoyr8AwU2rJDzlldUwcG-mBfbVhS247h4BygzDZ9jdLJVGlbDw5ojyEeejq0JbinbjRiFma7jlbgAl73_pWyQ9YqXXvY_Z63yePF-cPpVXR7f3l9Or-NjJBCRVmpeBlLfFOSidRkUvFUQVwIowvFSqlkauJsJljJtcT_YSLWwoCpikSaWJVimxxOXnzsywA-5I31BmqsHbrB55gqZgw_ViB68AdddINrsTqk0I01zEbqaKKM67x3UOW9s412y5yzfOxVjr3Kv3qF7P63cSgaKH_Jn-YgcDIBb7aG5f-mfH5zPSk_Aft4oHw</recordid><startdate>202001</startdate><enddate>202001</enddate><creator>Pathare, Amruta D. S.</creator><creator>Hinduja, Indira</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-5608-2370</orcidid></search><sort><creationdate>202001</creationdate><title>Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization</title><author>Pathare, Amruta D. S. ; Hinduja, Indira</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3536-9d61d459377938c956186e4b3cab60d5658c49230d1a5319034a3cecfb75c46d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Chorionic gonadotropin</topic><topic>controlled ovarian stimulation</topic><topic>CpG islands</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA fingerprinting</topic><topic>DNA methylation</topic><topic>DNA microarrays</topic><topic>Endometrium</topic><topic>fertilization in vitro</topic><topic>Gene expression</topic><topic>gene expression profiling</topic><topic>Genomes</topic><topic>Gonadotropins</topic><topic>Immune response</topic><topic>Immunology</topic><topic>In vitro fertilization</topic><topic>Inflammation</topic><topic>Menstrual cycle</topic><topic>Pituitary (anterior)</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pathare, Amruta D. S.</creatorcontrib><creatorcontrib>Hinduja, Indira</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>American journal of reproductive immunology (1989)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pathare, Amruta D. S.</au><au>Hinduja, Indira</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization</atitle><jtitle>American journal of reproductive immunology (1989)</jtitle><addtitle>Am J Reprod Immunol</addtitle><date>2020-01</date><risdate>2020</risdate><volume>83</volume><issue>1</issue><spage>e13196</spage><epage>n/a</epage><pages>e13196-n/a</pages><issn>1046-7408</issn><eissn>1600-0897</eissn><abstract>Problem
DNA methylation profile in mid‐secretory phase of endometrium is reported to be varied from other phases in natural menstrual cycle. Therefore, we intended to study the impairment in endometrial receptivity by performing whole‐genome methylation and gene expression profiling in endometrium of recurrent implantation failure patients (RIF) during IVF under controlled ovarian stimulation (COS).
Method of study
Endometrial biopsies were collected from IVF‐RIF patients (cases, n = 6) and healthy fertile oocyte donors (controls, n = 6) undergoing COS after 6/7th day of human chorionic gonadotropin administration. The whole‐genome methylation and gene expression microarray were performed and analysed by GenomeStudio software (P < .05 by Illumina Custom Model), whereas the enrichment analysis was performed using “Database for Annotation, Visualization and Integrated Discovery” (DAVID, V6.8). Significant differentially methylated genes were correlated with dys‐regulated genes using Pearson's correlation.
Results
Differential methylation in RIF patients revealed 448 CpG sites. The enrichment analysis showed aberrant methylation in genes involved in immunological response and G protein activity. Methylation in NLRP2 gene in inflammatory pathway had significant negative correlation with gene expression (P = .008), whereas SERPINA5 gene that is already known to be involved in endometrial receptivity was observed to be hypomethylated in promoter region with highest delta beta value and up‐regulated in gene expression analysis.
Conclusion
The aberrant methylation of genes involved in immunological functions and G protein activation was found to be prevalent which might suggest a role in endometrial receptivity. However, the findings need to be further validated on a larger cohort of IVF‐RIF patients.</abstract><cop>Denmark</cop><pub>Wiley Subscription Services, Inc</pub><pmid>31595580</pmid><doi>10.1111/aji.13196</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5608-2370</orcidid></addata></record> |
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| ispartof | American journal of reproductive immunology (1989), 2020-01, Vol.83 (1), p.e13196-n/a |
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| language | eng |
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| source | Wiley Online Library Journals Frontfile Complete |
| subjects | Chorionic gonadotropin controlled ovarian stimulation CpG islands Deoxyribonucleic acid DNA DNA fingerprinting DNA methylation DNA microarrays Endometrium fertilization in vitro Gene expression gene expression profiling Genomes Gonadotropins Immune response Immunology In vitro fertilization Inflammation Menstrual cycle Pituitary (anterior) |
| title | Aberrant DNA methylation profiling affecting the endometrial receptivity in recurrent implantation failure patients undergoing in vitro fertilization |
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