Deoxyribonucleic acid methylation signatures in sperm deoxyribonucleic acid fragmentation

To evaluate Deoxyribonucleic acid (DNA) methylation patterns in sperm from men with differential levels of sperm DNA fragmentation index (DFI). Prospective study. University-affiliated reproductive medicine center. A total of 278 male patients consulting for couple infertility were recruited from th...

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Veröffentlicht in:Fertility and sterility 2021-11, Vol.116 (5), p.1297-1307
Hauptverfasser: Zhu, Weijian, Jiang, Lei, Pan, Chengshuang, Sun, Junhui, Huang, Xuefeng, Ni, Wuhua
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container_issue 5
container_start_page 1297
container_title Fertility and sterility
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creator Zhu, Weijian
Jiang, Lei
Pan, Chengshuang
Sun, Junhui
Huang, Xuefeng
Ni, Wuhua
description To evaluate Deoxyribonucleic acid (DNA) methylation patterns in sperm from men with differential levels of sperm DNA fragmentation index (DFI). Prospective study. University-affiliated reproductive medicine center. A total of 278 male patients consulting for couple infertility were recruited from the First Affiliated Hospital of Wenzhou Medical University. None. Genome-wide DNA methylation analysis was performed using Infinium MethylationEPIC BeadChip on spermatozoal DNA from 20 male patients. Differentially methylated regions (DMRs) were identified and validated using targeted bisulfite amplicon sequencing in spermatozoal DNA from 266 males. Unsupervised hierarchical clustering analysis revealed three main clusters corresponding to sperm DFI levels (low, medium, or high). Between-cluster comparisons identified 959 (medium–low), 738 (high–medium), and 937 (high–low) DMRs. Sixty-six DMRs were validated in the 266-sample cohort, of which nine CpG fragments corresponding to nine genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1, and TEX12) exhibited significantly altered methylation in those with high DFI (≥25%) compared with those with low DFI (
doi_str_mv 10.1016/j.fertnstert.2021.06.025
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Prospective study. University-affiliated reproductive medicine center. A total of 278 male patients consulting for couple infertility were recruited from the First Affiliated Hospital of Wenzhou Medical University. None. Genome-wide DNA methylation analysis was performed using Infinium MethylationEPIC BeadChip on spermatozoal DNA from 20 male patients. Differentially methylated regions (DMRs) were identified and validated using targeted bisulfite amplicon sequencing in spermatozoal DNA from 266 males. Unsupervised hierarchical clustering analysis revealed three main clusters corresponding to sperm DFI levels (low, medium, or high). Between-cluster comparisons identified 959 (medium–low), 738 (high–medium), and 937 (high–low) DMRs. Sixty-six DMRs were validated in the 266-sample cohort, of which nine CpG fragments corresponding to nine genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1, and TEX12) exhibited significantly altered methylation in those with high DFI (≥25%) compared with those with low DFI (&lt;25%). We identified and validated a distinct DNA methylation signature associated with sperm DNA damage in a large, unselected cohort. These results indicate that sperm DNA damage may affect DNA methylation patterns in human sperm. Firmas de metilación del ácido desoxirribonucleico en la fragmentación del ácido desoxirribonucleico de los espermatozoides. Evaluar los patrones de metilación del ácido desoxirribonucleico (ADN) en espermatozoides de hombres con niveles diferenciales de índice de fragmentación del ADN espermático (DFI). Estudio prospectivo. Centro de medicina reproductiva afiliado a universidad. Un total de 278 pacientes varones que consultaban por infertilidad de pareja fueron reclutados en el Primer Hospital Afiliado de la Universidad Médica de Wenzhou. Ninguna. El análisis de metilación del ADN de todo el genoma se realizó utilizando Infinium MethylationEPIC BeadChip en el ADN de espermatozoides de 20 pacientes varones. Se identificaron y validaron regiones diferencialmente metiladas (DMR) mediante la secuenciación de amplicones de bisulfito dirigida en el ADN de espermatozoides de 266 varones. El análisis de agrupamiento jerárquico no supervisado reveló tres grupos principales correspondientes a los niveles de DFI de esperma (bajo, medio o alto). Las comparaciones entre grupos identificaron 959 (medio-bajo), 738 (alto-medio) y 937 (alto-bajo) DMR. Se validaron 66 DMR en la cohorte de 266 muestras, de los cuales nueve fragmentos CpG correspondientes a nueve genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1 y TEX12) exhibieron una metilación significativamente alterada en aquellos con alta DFI (R25%) en comparación con aquellos con DFI bajo (&lt;25%). Identificamos y validamos una firma de metilación del ADN distinta asociada con el daño del ADN de los espermatozoides en una cohorte grande no seleccionada. 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Sixty-six DMRs were validated in the 266-sample cohort, of which nine CpG fragments corresponding to nine genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1, and TEX12) exhibited significantly altered methylation in those with high DFI (≥25%) compared with those with low DFI (&lt;25%). We identified and validated a distinct DNA methylation signature associated with sperm DNA damage in a large, unselected cohort. These results indicate that sperm DNA damage may affect DNA methylation patterns in human sperm. Firmas de metilación del ácido desoxirribonucleico en la fragmentación del ácido desoxirribonucleico de los espermatozoides. Evaluar los patrones de metilación del ácido desoxirribonucleico (ADN) en espermatozoides de hombres con niveles diferenciales de índice de fragmentación del ADN espermático (DFI). Estudio prospectivo. Centro de medicina reproductiva afiliado a universidad. 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Se validaron 66 DMR en la cohorte de 266 muestras, de los cuales nueve fragmentos CpG correspondientes a nueve genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1 y TEX12) exhibieron una metilación significativamente alterada en aquellos con alta DFI (R25%) en comparación con aquellos con DFI bajo (&lt;25%). Identificamos y validamos una firma de metilación del ADN distinta asociada con el daño del ADN de los espermatozoides en una cohorte grande no seleccionada. 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Prospective study. University-affiliated reproductive medicine center. A total of 278 male patients consulting for couple infertility were recruited from the First Affiliated Hospital of Wenzhou Medical University. None. Genome-wide DNA methylation analysis was performed using Infinium MethylationEPIC BeadChip on spermatozoal DNA from 20 male patients. Differentially methylated regions (DMRs) were identified and validated using targeted bisulfite amplicon sequencing in spermatozoal DNA from 266 males. Unsupervised hierarchical clustering analysis revealed three main clusters corresponding to sperm DFI levels (low, medium, or high). Between-cluster comparisons identified 959 (medium–low), 738 (high–medium), and 937 (high–low) DMRs. Sixty-six DMRs were validated in the 266-sample cohort, of which nine CpG fragments corresponding to nine genes (BLCAP, DIRAS3, FAM50B, GNAS, MEST, TSPAN32, PSMA8, SYCP1, and TEX12) exhibited significantly altered methylation in those with high DFI (≥25%) compared with those with low DFI (&lt;25%). We identified and validated a distinct DNA methylation signature associated with sperm DNA damage in a large, unselected cohort. These results indicate that sperm DNA damage may affect DNA methylation patterns in human sperm. Firmas de metilación del ácido desoxirribonucleico en la fragmentación del ácido desoxirribonucleico de los espermatozoides. Evaluar los patrones de metilación del ácido desoxirribonucleico (ADN) en espermatozoides de hombres con niveles diferenciales de índice de fragmentación del ADN espermático (DFI). Estudio prospectivo. Centro de medicina reproductiva afiliado a universidad. Un total de 278 pacientes varones que consultaban por infertilidad de pareja fueron reclutados en el Primer Hospital Afiliado de la Universidad Médica de Wenzhou. Ninguna. El análisis de metilación del ADN de todo el genoma se realizó utilizando Infinium MethylationEPIC BeadChip en el ADN de espermatozoides de 20 pacientes varones. Se identificaron y validaron regiones diferencialmente metiladas (DMR) mediante la secuenciación de amplicones de bisulfito dirigida en el ADN de espermatozoides de 266 varones. El análisis de agrupamiento jerárquico no supervisado reveló tres grupos principales correspondientes a los niveles de DFI de esperma (bajo, medio o alto). Las comparaciones entre grupos identificaron 959 (medio-bajo), 738 (alto-medio) y 937 (alto-bajo) DMR. 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source Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present); Alma/SFX Local Collection
subjects DNA methylation
sperm DNA damage
sperm DNA fragmentation
spermatozoa
title Deoxyribonucleic acid methylation signatures in sperm deoxyribonucleic acid fragmentation
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