The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study
Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes...
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| Veröffentlicht in: | Environmental science & technology 2024-07, Vol.58 (26), p.11320-11330 |
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| creator | Chen, Jiaxian Zhu, Haijun Chen, Yafei Pan, Shuqin Liang, Hong Song, Xiuxia Wu, Qihan Yuan, Wei Miao, Maohua Wang, Ziliang |
| description | Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children’s digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother–child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure. |
| doi_str_mv | 10.1021/acs.est.4c03764 |
| format | Article |
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Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children’s digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother–child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.</description><identifier>ISSN: 0013-936X</identifier><identifier>ISSN: 1520-5851</identifier><identifier>EISSN: 1520-5851</identifier><identifier>DOI: 10.1021/acs.est.4c03764</identifier><identifier>PMID: 38898774</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Adult ; Benzhydryl Compounds ; Birth Cohort ; Bisphenol A ; Child, Preschool ; Children ; Cohort analysis ; Cohort Studies ; Deoxyribonucleic acid ; DNA ; DNA Methylation ; Ecotoxicology and Public Health ; Exposure ; Female ; Fingers - anatomy & histology ; Genes ; Growth factors ; Humans ; Male ; Maternal Exposure ; Phenols - toxicity ; Placenta ; Placenta - drug effects ; Placenta - metabolism ; Pregnancy ; Prenatal experience ; Prenatal Exposure Delayed Effects ; Protocadherin ; Ratios ; Regression analysis ; Regression models ; Reproduction - drug effects ; Reproductive health</subject><ispartof>Environmental science & technology, 2024-07, Vol.58 (26), p.11320-11330</ispartof><rights>2024 American Chemical Society</rights><rights>Copyright American Chemical Society Jul 2, 2024</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-a245t-6b4b8e2a632bd0d286e1c50c5990c990ae96abc238e9bbcd35c76f661c9764343</cites><orcidid>0000-0002-3430-9167 ; 0000-0002-1122-6481 ; 0000-0003-4375-4964</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.est.4c03764$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.est.4c03764$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>315,781,785,2766,27081,27929,27930,56743,56793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38898774$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Jiaxian</creatorcontrib><creatorcontrib>Zhu, Haijun</creatorcontrib><creatorcontrib>Chen, Yafei</creatorcontrib><creatorcontrib>Pan, Shuqin</creatorcontrib><creatorcontrib>Liang, Hong</creatorcontrib><creatorcontrib>Song, Xiuxia</creatorcontrib><creatorcontrib>Wu, Qihan</creatorcontrib><creatorcontrib>Yuan, Wei</creatorcontrib><creatorcontrib>Miao, Maohua</creatorcontrib><creatorcontrib>Wang, Ziliang</creatorcontrib><title>The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study</title><title>Environmental science & technology</title><addtitle>Environ. Sci. Technol</addtitle><description>Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children’s digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother–child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.</description><subject>Adult</subject><subject>Benzhydryl Compounds</subject><subject>Birth Cohort</subject><subject>Bisphenol A</subject><subject>Child, Preschool</subject><subject>Children</subject><subject>Cohort analysis</subject><subject>Cohort Studies</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Ecotoxicology and Public Health</subject><subject>Exposure</subject><subject>Female</subject><subject>Fingers - anatomy & histology</subject><subject>Genes</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Male</subject><subject>Maternal Exposure</subject><subject>Phenols - toxicity</subject><subject>Placenta</subject><subject>Placenta - drug effects</subject><subject>Placenta - metabolism</subject><subject>Pregnancy</subject><subject>Prenatal experience</subject><subject>Prenatal Exposure Delayed Effects</subject><subject>Protocadherin</subject><subject>Ratios</subject><subject>Regression analysis</subject><subject>Regression models</subject><subject>Reproduction - drug effects</subject><subject>Reproductive health</subject><issn>0013-936X</issn><issn>1520-5851</issn><issn>1520-5851</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUFv0zAUxy0EYqVw5oaexAUJpXPixIm5hW4MpAFTGRK3yHFem0yu3dmOtn47PhrOWnZA4mBZln_v9-z3J-R1ShcpzdJTqfwCfVjkirKS50_ILC0ymhRVkT4lM0pTlgjGf52QF97fUEozRqvn5IRVlajKMp-R39c9wspqBLuGKy0VmiA1nH2r4SuGfq9lGKwBGWCFO2e7UU3nZIXxAju4QIMeBgO191YND7CHFsMdooErh0ZOuo-D3_VorIbaSG03Yyw6v99ZPzoEaToI8RVnw2aIbSbHZFz2g-6iYOpdbxDyD1BHkQs9LG1vXYAfYez2L8mztdQeXx33Ofn56fx6-Tm5_H7xZVlfJjLLi5DwNm8rzCRnWdvRLqs4pqqgqhCCqrgkCi5blbEKRduqjhWq5GvOUyXiXFnO5uTdwRuncBvfH5rt4BVqLQ3a0TeMlrTKChFHPidv_0Fv7Ojixx8oXooYhIjU6YFSznrvcN3s3LCVbt-ktJnCbWK4zVR9DDdWvDl6x3aL3SP_N80IvD8AU-Vjz__p_gAyH7Dr</recordid><startdate>20240702</startdate><enddate>20240702</enddate><creator>Chen, Jiaxian</creator><creator>Zhu, Haijun</creator><creator>Chen, Yafei</creator><creator>Pan, Shuqin</creator><creator>Liang, Hong</creator><creator>Song, Xiuxia</creator><creator>Wu, Qihan</creator><creator>Yuan, Wei</creator><creator>Miao, Maohua</creator><creator>Wang, Ziliang</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7ST</scope><scope>7T7</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>SOI</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-3430-9167</orcidid><orcidid>https://orcid.org/0000-0002-1122-6481</orcidid><orcidid>https://orcid.org/0000-0003-4375-4964</orcidid></search><sort><creationdate>20240702</creationdate><title>The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study</title><author>Chen, Jiaxian ; Zhu, Haijun ; Chen, Yafei ; Pan, Shuqin ; Liang, Hong ; Song, Xiuxia ; Wu, Qihan ; Yuan, Wei ; Miao, Maohua ; Wang, Ziliang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a245t-6b4b8e2a632bd0d286e1c50c5990c990ae96abc238e9bbcd35c76f661c9764343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Benzhydryl Compounds</topic><topic>Birth Cohort</topic><topic>Bisphenol A</topic><topic>Child, Preschool</topic><topic>Children</topic><topic>Cohort analysis</topic><topic>Cohort Studies</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Ecotoxicology and Public Health</topic><topic>Exposure</topic><topic>Female</topic><topic>Fingers - anatomy & histology</topic><topic>Genes</topic><topic>Growth factors</topic><topic>Humans</topic><topic>Male</topic><topic>Maternal Exposure</topic><topic>Phenols - toxicity</topic><topic>Placenta</topic><topic>Placenta - drug effects</topic><topic>Placenta - metabolism</topic><topic>Pregnancy</topic><topic>Prenatal experience</topic><topic>Prenatal Exposure Delayed Effects</topic><topic>Protocadherin</topic><topic>Ratios</topic><topic>Regression analysis</topic><topic>Regression models</topic><topic>Reproduction - drug effects</topic><topic>Reproductive health</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Jiaxian</creatorcontrib><creatorcontrib>Zhu, Haijun</creatorcontrib><creatorcontrib>Chen, Yafei</creatorcontrib><creatorcontrib>Pan, Shuqin</creatorcontrib><creatorcontrib>Liang, Hong</creatorcontrib><creatorcontrib>Song, Xiuxia</creatorcontrib><creatorcontrib>Wu, Qihan</creatorcontrib><creatorcontrib>Yuan, Wei</creatorcontrib><creatorcontrib>Miao, Maohua</creatorcontrib><creatorcontrib>Wang, Ziliang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Environment Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Environmental science & technology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Jiaxian</au><au>Zhu, Haijun</au><au>Chen, Yafei</au><au>Pan, Shuqin</au><au>Liang, Hong</au><au>Song, Xiuxia</au><au>Wu, Qihan</au><au>Yuan, Wei</au><au>Miao, Maohua</au><au>Wang, Ziliang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study</atitle><jtitle>Environmental science & technology</jtitle><addtitle>Environ. Sci. Technol</addtitle><date>2024-07-02</date><risdate>2024</risdate><volume>58</volume><issue>26</issue><spage>11320</spage><epage>11330</epage><pages>11320-11330</pages><issn>0013-936X</issn><issn>1520-5851</issn><eissn>1520-5851</eissn><abstract>Placental DNA methylation (DNAm) may be a potential mechanism underlying the effects of prenatal bisphenol analogues (BPs) exposure on reproductive health. Based on the Shanghai-Minhang Birth Cohort Study (S-MBCS), this study investigated associations of placental DNAm at reproduction-related genes with prenatal BPs exposure and children’s digit ratios at age 4 using multiple linear regression models, and mediation analysis was further used to examine the mediating role of placental DNAm in the associations between prenatal BPs exposure and digit ratios among 345 mother–child pairs. Prenatal exposure to bisphenol A (BPA) was associated with hypermethylation at Protocadherin 8 (PCDH8), RBMX Like 2 (RBMXL2), and Sperm Acrosome Associated 1 (SPACA1), while bisphenol F (BPF) exposure was associated with higher methylation levels of Fibroblast Growth Factor 13 (FGF13). Consistent patterns were found in associations between higher DNAm at the 4 genes and increased digit ratios. Further mediation analysis showed that about 15% of the effect of BPF exposure on increased digit ratios was mediated by placental FGF13 methylation. In conclusion, the altered placental DNAm status might be a mediator underlying the feminizing effect of prenatal BPs exposure.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>38898774</pmid><doi>10.1021/acs.est.4c03764</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0002-3430-9167</orcidid><orcidid>https://orcid.org/0000-0002-1122-6481</orcidid><orcidid>https://orcid.org/0000-0003-4375-4964</orcidid></addata></record> |
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| subjects | Adult Benzhydryl Compounds Birth Cohort Bisphenol A Child, Preschool Children Cohort analysis Cohort Studies Deoxyribonucleic acid DNA DNA Methylation Ecotoxicology and Public Health Exposure Female Fingers - anatomy & histology Genes Growth factors Humans Male Maternal Exposure Phenols - toxicity Placenta Placenta - drug effects Placenta - metabolism Pregnancy Prenatal experience Prenatal Exposure Delayed Effects Protocadherin Ratios Regression analysis Regression models Reproduction - drug effects Reproductive health |
| title | The Role of Placental DNA Methylation at Reproduction-Related Genes in Associations between Prenatal Bisphenol Analogues Exposure and the Digit Ratio in Children at Age 4: A Birth Cohort Study |
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