Male obesity effects on sperm and next-generation cord blood DNA methylation
The prevalence of metabolic disorders, in particular obesity has dramatically increased worldwide. Genetic variants explain only a minor part of the obesity epidemic induced by physical inactivity and over-nutrition. Epidemiological studies in humans and animal models indicate that epigenetic change...
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| description | The prevalence of metabolic disorders, in particular obesity has dramatically increased worldwide. Genetic variants explain only a minor part of the obesity epidemic induced by physical inactivity and over-nutrition. Epidemiological studies in humans and animal models indicate that epigenetic changes associated with adverse parental and/or intrauterine factors may contribute to the missing heritability of metabolic disorders. Possible adverse paternal effects are likely transmitted by sperm to the next-generation. To investigate this hypothesis, we have systematically analyzed the effects of male body mass index (BMI) on sperm epigenome and its association with next-generation fetal cord blood (FCB) DNA methylation. Methylation levels of maternally imprinted (PEG1, PEG4, PEG5, and PEG10), paternally imprinted (H19-IG DMR, IGF2-DMR0, and MEG3-IG DMR) regions, and obesity-related non-imprinted HIF3A gene were quantified by bisulphite pyrosequencing in sperm samples of 294 human donors undergoing in vitro fertilization or intracytoplasmic sperm injection, and in 113 FCBs of the resulting offspring. Multivariable regression analyses revealed that MEG3 intergenic differentially methylated region (IG DMR) showed positive correlation between sperm methylation and donor's BMI. A gender-specific correlation between paternal BMI and FCB methylation was observed for MEG3-IG DMR, HIF3A, and IGF2-DMR0. The former two genes displayed same directional nominal association (as sperm) between paternal BMI and FCB methylation in male offspring. Hypomethylation of IGF2-DMR0 with increased paternal BMI was observed in FCBs from female offsprings. Our results suggest that male obesity is nominally associated with modification of sperm DNA methylome in humans, which may affect the epigenome of the next-generation. Nevertheless, it is important to note that none of the associated p-values survived multiple testing adjustments. Future work should test the effect of associated methylation aberrations in the offspring as DNA methylation was shown to control expression and/or imprint establishment across the studied genes. |
| doi_str_mv | 10.1371/journal.pone.0218615 |
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Genetic variants explain only a minor part of the obesity epidemic induced by physical inactivity and over-nutrition. Epidemiological studies in humans and animal models indicate that epigenetic changes associated with adverse parental and/or intrauterine factors may contribute to the missing heritability of metabolic disorders. Possible adverse paternal effects are likely transmitted by sperm to the next-generation. To investigate this hypothesis, we have systematically analyzed the effects of male body mass index (BMI) on sperm epigenome and its association with next-generation fetal cord blood (FCB) DNA methylation. Methylation levels of maternally imprinted (PEG1, PEG4, PEG5, and PEG10), paternally imprinted (H19-IG DMR, IGF2-DMR0, and MEG3-IG DMR) regions, and obesity-related non-imprinted HIF3A gene were quantified by bisulphite pyrosequencing in sperm samples of 294 human donors undergoing in vitro fertilization or intracytoplasmic sperm injection, and in 113 FCBs of the resulting offspring. Multivariable regression analyses revealed that MEG3 intergenic differentially methylated region (IG DMR) showed positive correlation between sperm methylation and donor's BMI. A gender-specific correlation between paternal BMI and FCB methylation was observed for MEG3-IG DMR, HIF3A, and IGF2-DMR0. The former two genes displayed same directional nominal association (as sperm) between paternal BMI and FCB methylation in male offspring. Hypomethylation of IGF2-DMR0 with increased paternal BMI was observed in FCBs from female offsprings. Our results suggest that male obesity is nominally associated with modification of sperm DNA methylome in humans, which may affect the epigenome of the next-generation. Nevertheless, it is important to note that none of the associated p-values survived multiple testing adjustments. Future work should test the effect of associated methylation aberrations in the offspring as DNA methylation was shown to control expression and/or imprint establishment across the studied genes.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0218615</identifier><identifier>PMID: 31246962</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal models ; Animals ; Apoptosis Regulatory Proteins - genetics ; Biology and life sciences ; Blood ; Body mass ; Body Mass Index ; Body size ; Cord blood ; Correlation ; Deoxyribonucleic acid ; Disorders ; DNA ; DNA Methylation ; Epidemics ; Epidemiology ; Epigenesis, Genetic ; Epigenetic inheritance ; Epigenetics ; Female ; Fertilization in vitro ; Fetal Blood - metabolism ; Fetuses ; Gender ; Gene expression ; Genes ; Genetic diversity ; Genetic variance ; Genomic Imprinting ; Health aspects ; Heritability ; High-Throughput Nucleotide Sequencing ; Humans ; Immunoglobulins ; In vitro fertilization ; Insulin-like growth factor II ; Insulin-Like Growth Factor II - genetics ; Male ; Medicine and Health Sciences ; Metabolic diseases ; Metabolic disorders ; Methylation ; Nutrition ; Obesity ; Obesity - blood ; Obesity - genetics ; Obesity - pathology ; Offspring ; Parenting ; Paternal effects ; Physical Sciences ; Prevalence studies (Epidemiology) ; Regression analysis ; Repressor Proteins - genetics ; Research and Analysis Methods ; RNA, Long Noncoding - genetics ; Sperm ; Spermatozoa - metabolism</subject><ispartof>PloS one, 2019-06, Vol.14 (6), p.e0218615-e0218615</ispartof><rights>COPYRIGHT 2019 Public Library of Science</rights><rights>2019 Potabattula et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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Genetic variants explain only a minor part of the obesity epidemic induced by physical inactivity and over-nutrition. Epidemiological studies in humans and animal models indicate that epigenetic changes associated with adverse parental and/or intrauterine factors may contribute to the missing heritability of metabolic disorders. Possible adverse paternal effects are likely transmitted by sperm to the next-generation. To investigate this hypothesis, we have systematically analyzed the effects of male body mass index (BMI) on sperm epigenome and its association with next-generation fetal cord blood (FCB) DNA methylation. Methylation levels of maternally imprinted (PEG1, PEG4, PEG5, and PEG10), paternally imprinted (H19-IG DMR, IGF2-DMR0, and MEG3-IG DMR) regions, and obesity-related non-imprinted HIF3A gene were quantified by bisulphite pyrosequencing in sperm samples of 294 human donors undergoing in vitro fertilization or intracytoplasmic sperm injection, and in 113 FCBs of the resulting offspring. Multivariable regression analyses revealed that MEG3 intergenic differentially methylated region (IG DMR) showed positive correlation between sperm methylation and donor's BMI. A gender-specific correlation between paternal BMI and FCB methylation was observed for MEG3-IG DMR, HIF3A, and IGF2-DMR0. The former two genes displayed same directional nominal association (as sperm) between paternal BMI and FCB methylation in male offspring. Hypomethylation of IGF2-DMR0 with increased paternal BMI was observed in FCBs from female offsprings. Our results suggest that male obesity is nominally associated with modification of sperm DNA methylome in humans, which may affect the epigenome of the next-generation. Nevertheless, it is important to note that none of the associated p-values survived multiple testing adjustments. Future work should test the effect of associated methylation aberrations in the offspring as DNA methylation was shown to control expression and/or imprint establishment across the studied genes.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Apoptosis Regulatory Proteins - genetics</subject><subject>Biology and life sciences</subject><subject>Blood</subject><subject>Body mass</subject><subject>Body Mass Index</subject><subject>Body size</subject><subject>Cord blood</subject><subject>Correlation</subject><subject>Deoxyribonucleic acid</subject><subject>Disorders</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Epidemics</subject><subject>Epidemiology</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Fertilization in vitro</subject><subject>Fetal Blood - metabolism</subject><subject>Fetuses</subject><subject>Gender</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Genetic diversity</subject><subject>Genetic variance</subject><subject>Genomic Imprinting</subject><subject>Health aspects</subject><subject>Heritability</subject><subject>High-Throughput Nucleotide Sequencing</subject><subject>Humans</subject><subject>Immunoglobulins</subject><subject>In vitro fertilization</subject><subject>Insulin-like growth factor II</subject><subject>Insulin-Like Growth Factor II - genetics</subject><subject>Male</subject><subject>Medicine and Health Sciences</subject><subject>Metabolic diseases</subject><subject>Metabolic disorders</subject><subject>Methylation</subject><subject>Nutrition</subject><subject>Obesity</subject><subject>Obesity - blood</subject><subject>Obesity - genetics</subject><subject>Obesity - pathology</subject><subject>Offspring</subject><subject>Parenting</subject><subject>Paternal effects</subject><subject>Physical Sciences</subject><subject>Prevalence studies (Epidemiology)</subject><subject>Regression analysis</subject><subject>Repressor Proteins - genetics</subject><subject>Research and Analysis Methods</subject><subject>RNA, Long Noncoding - genetics</subject><subject>Sperm</subject><subject>Spermatozoa - metabolism</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNktuO0zAQhiMEYpfCGyCIhITgoiU-xIlvkKpdDpUKK3G6tRx73KZy4mInaPv2ONvsqkF7gXxhy_PNP_bMnyTPUbZApEDvdq73rbSLvWthkWFUMpQ_SM4RJ3jOcEYenpzPkich7LIsJyVjj5MzgjBlnOHzZP1FWkhdBaHuDikYA6oLqWvTsAffpLLVaQvX3XwDLXjZ1TGinNdpZZ3T6eXXZdpAtz3Ym9DT5JGRNsCzcZ8lPz9--HHxeb6--rS6WK7nqsjLbo4YMznnRVkZjREGXUgiC8MVmJJRSTjHLCMKYU1xQXmO87LKSE5LSXAlkSSz5OVRd29dEGMjgsCYloSVZfzmLFkdCe3kTux93Uh_EE7W4ubC-Y2QvquVBUG10UxTwxhWVBHNeVZJQpTkoIhBOmq9H6v1VQNaQdt5aSei00hbb8XG_REs50XGUBR4Mwp497uH0ImmDgqslS24fnh3njFaxJZE9NU_6P2_G6lNHJ6oW-NiXTWIimXOEaKc50PZxT1UXBqaWkXXmDreTxLeThIi08XZb2Qfglh9__b_7NWvKfv6hN2CtN02ONsPlglTkB5B5V0IHsxdk1EmBtPfdkMMphej6WPai9MB3SXdupz8BbgF-0Y</recordid><startdate>20190627</startdate><enddate>20190627</enddate><creator>Potabattula, Ramya</creator><creator>Dittrich, Marcus</creator><creator>Schorsch, Martin</creator><creator>Hahn, Thomas</creator><creator>Haaf, Thomas</creator><creator>El Hajj, Nady</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0003-3420-8531</orcidid></search><sort><creationdate>20190627</creationdate><title>Male obesity effects on sperm and next-generation cord blood DNA methylation</title><author>Potabattula, Ramya ; Dittrich, Marcus ; Schorsch, Martin ; Hahn, Thomas ; Haaf, Thomas ; El Hajj, Nady</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-166f59978bfd212ed7a3a7f9cef864a3992603c12d427495258b03548a32ba1a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Apoptosis Regulatory Proteins - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Potabattula, Ramya</au><au>Dittrich, Marcus</au><au>Schorsch, Martin</au><au>Hahn, Thomas</au><au>Haaf, Thomas</au><au>El Hajj, Nady</au><au>Böttcher, Yvonne</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Male obesity effects on sperm and next-generation cord blood DNA methylation</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2019-06-27</date><risdate>2019</risdate><volume>14</volume><issue>6</issue><spage>e0218615</spage><epage>e0218615</epage><pages>e0218615-e0218615</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The prevalence of metabolic disorders, in particular obesity has dramatically increased worldwide. Genetic variants explain only a minor part of the obesity epidemic induced by physical inactivity and over-nutrition. Epidemiological studies in humans and animal models indicate that epigenetic changes associated with adverse parental and/or intrauterine factors may contribute to the missing heritability of metabolic disorders. Possible adverse paternal effects are likely transmitted by sperm to the next-generation. To investigate this hypothesis, we have systematically analyzed the effects of male body mass index (BMI) on sperm epigenome and its association with next-generation fetal cord blood (FCB) DNA methylation. Methylation levels of maternally imprinted (PEG1, PEG4, PEG5, and PEG10), paternally imprinted (H19-IG DMR, IGF2-DMR0, and MEG3-IG DMR) regions, and obesity-related non-imprinted HIF3A gene were quantified by bisulphite pyrosequencing in sperm samples of 294 human donors undergoing in vitro fertilization or intracytoplasmic sperm injection, and in 113 FCBs of the resulting offspring. Multivariable regression analyses revealed that MEG3 intergenic differentially methylated region (IG DMR) showed positive correlation between sperm methylation and donor's BMI. A gender-specific correlation between paternal BMI and FCB methylation was observed for MEG3-IG DMR, HIF3A, and IGF2-DMR0. The former two genes displayed same directional nominal association (as sperm) between paternal BMI and FCB methylation in male offspring. Hypomethylation of IGF2-DMR0 with increased paternal BMI was observed in FCBs from female offsprings. Our results suggest that male obesity is nominally associated with modification of sperm DNA methylome in humans, which may affect the epigenome of the next-generation. Nevertheless, it is important to note that none of the associated p-values survived multiple testing adjustments. Future work should test the effect of associated methylation aberrations in the offspring as DNA methylation was shown to control expression and/or imprint establishment across the studied genes.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>31246962</pmid><doi>10.1371/journal.pone.0218615</doi><tpages>e0218615</tpages><orcidid>https://orcid.org/0000-0003-3420-8531</orcidid><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_2248368805 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Public Library of Science (PLoS); PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Analysis Animal models Animals Apoptosis Regulatory Proteins - genetics Biology and life sciences Blood Body mass Body Mass Index Body size Cord blood Correlation Deoxyribonucleic acid Disorders DNA DNA Methylation Epidemics Epidemiology Epigenesis, Genetic Epigenetic inheritance Epigenetics Female Fertilization in vitro Fetal Blood - metabolism Fetuses Gender Gene expression Genes Genetic diversity Genetic variance Genomic Imprinting Health aspects Heritability High-Throughput Nucleotide Sequencing Humans Immunoglobulins In vitro fertilization Insulin-like growth factor II Insulin-Like Growth Factor II - genetics Male Medicine and Health Sciences Metabolic diseases Metabolic disorders Methylation Nutrition Obesity Obesity - blood Obesity - genetics Obesity - pathology Offspring Parenting Paternal effects Physical Sciences Prevalence studies (Epidemiology) Regression analysis Repressor Proteins - genetics Research and Analysis Methods RNA, Long Noncoding - genetics Sperm Spermatozoa - metabolism |
| title | Male obesity effects on sperm and next-generation cord blood DNA methylation |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-15T11%3A44%3A44IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Male%20obesity%20effects%20on%20sperm%20and%20next-generation%20cord%20blood%20DNA%20methylation&rft.jtitle=PloS%20one&rft.au=Potabattula,%20Ramya&rft.date=2019-06-27&rft.volume=14&rft.issue=6&rft.spage=e0218615&rft.epage=e0218615&rft.pages=e0218615-e0218615&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0218615&rft_dat=%3Cgale_plos_%3EA591149951%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2248368805&rft_id=info:pmid/31246962&rft_galeid=A591149951&rft_doaj_id=oai_doaj_org_article_4dfd6d4f662c4c3d990ba33ca9ec3f1d&rfr_iscdi=true |