Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator
Abstract Background In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero ex...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-04-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-023-01473-1 |
| _version_ | 1797849952621166592 |
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| author | Guoying Wang Richard Xu Boyang Zhang Xiumei Hong Tami R. Bartell Colleen Pearson Liming Liang Xiaobin Wang |
| author_facet | Guoying Wang Richard Xu Boyang Zhang Xiumei Hong Tami R. Bartell Colleen Pearson Liming Liang Xiaobin Wang |
| author_sort | Guoying Wang |
| collection | DOAJ |
| description | Abstract Background In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population. Methods This study included 954 mother–newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package. Results 126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%. Conclusions In this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth. |
| first_indexed | 2024-04-09T18:53:36Z |
| format | Article |
| id | doaj.art-2f221507c8b44431a351c1cdcf92bf21 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-04-09T18:53:36Z |
| publishDate | 2023-04-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-2f221507c8b44431a351c1cdcf92bf212023-04-09T11:19:45ZengBMCClinical Epigenetics1868-70832023-04-011511910.1186/s13148-023-01473-1Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediatorGuoying Wang0Richard Xu1Boyang Zhang2Xiumei Hong3Tami R. Bartell4Colleen Pearson5Liming Liang6Xiaobin Wang7Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public HealthDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public HealthDepartment of Biostatistics, Johns Hopkins University Bloomberg School of Public HealthCenter on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public HealthPatrick M. Magoon Institute for Healthy Communities, Ann & Robert H. Lurie Children’s Hospital of ChicagoDepartment of Pediatrics, Boston University Chobanian & Avedisian School of Medicine and Boston Medical CenterDepartment of Epidemiology, Harvard T.H. Chan School of Public HealthCenter on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public HealthAbstract Background In utero exposure to diabetes has been shown to contribute to preterm birth, though the underlying biological mechanisms are yet to be fully elucidated. Fetal epigenetic variations established in utero may be a possible pathway. This study aimed to investigate whether in utero exposure to diabetes was associated with a change in newborn DNA methylation, and whether the identified CpG sites mediate the association between diabetes and preterm birth in a racially diverse birth cohort population. Methods This study included 954 mother–newborn pairs. Methylation levels in the cord blood were determined using the Illumina Infinium MethylationEPIC BeadChip 850 K array platform. In utero exposure to diabetes was defined by the presence of maternal pregestational or gestational diabetes. Preterm birth was defined as gestational age at birth less than 37 weeks. Linear regression analysis was employed to identify differentially methylated CpG sites. Differentially methylated regions were identified using the DMRcate Package. Results 126 (13%) newborns were born to mothers with diabetes in pregnancy and 173 (18%) newborns were born preterm, while 41 newborns were born both preterm and to mothers with diabetes in pregnancy. Genomic-wide CpG analysis found that eighteen CpG sites in cord blood were differentially methylated by maternal diabetes status at an FDR threshold of 5%. These significant CpG sites were mapped to 12 known genes, one of which was annotated to gene Major Histocompatibility Complex, Class II, DM Beta (HLA-DMB). Consistently, one of the two identified significant methylated regions overlapped with HLA-DMB. The identified differentially methylated CpG sites mediated the association between diabetes in pregnancy and preterm birth by 61%. Conclusions In this US birth cohort, we found that maternal diabetes was associated with altered fetal DNA methylation patterns, which substantially explained the link between diabetes and preterm birth.https://doi.org/10.1186/s13148-023-01473-1Cord bloodDiabetesDNA methylationIn uteroPreterm birth |
| spellingShingle | Guoying Wang Richard Xu Boyang Zhang Xiumei Hong Tami R. Bartell Colleen Pearson Liming Liang Xiaobin Wang Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator Clinical Epigenetics Cord blood Diabetes DNA methylation In utero Preterm birth |
| title | Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator |
| title_full | Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator |
| title_fullStr | Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator |
| title_full_unstemmed | Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator |
| title_short | Impact of intrauterine exposure to maternal diabetes on preterm birth: fetal DNA methylation alteration is an important mediator |
| title_sort | impact of intrauterine exposure to maternal diabetes on preterm birth fetal dna methylation alteration is an important mediator |
| topic | Cord blood Diabetes DNA methylation In utero Preterm birth |
| url | https://doi.org/10.1186/s13148-023-01473-1 |
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