Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence
Abstract Background Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Clinical Epigenetics |
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| Online Access: | https://doi.org/10.1186/s13148-023-01610-w |
| _version_ | 1827327158175924224 |
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| author | Ivona Bečeheli Marina Horvatiček Maja Perić Barbara Nikolić Cyrielle Holuka Marija Klasić Marina Ivanišević Mirta Starčević Gernot Desoye Dubravka Hranilović Jonathan D. Turner Jasminka Štefulj |
| author_facet | Ivona Bečeheli Marina Horvatiček Maja Perić Barbara Nikolić Cyrielle Holuka Marija Klasić Marina Ivanišević Mirta Starčević Gernot Desoye Dubravka Hranilović Jonathan D. Turner Jasminka Štefulj |
| author_sort | Ivona Bečeheli |
| collection | DOAJ |
| description | Abstract Background Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database. Results None of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites. Conclusions Methylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence. |
| first_indexed | 2024-03-07T14:55:59Z |
| format | Article |
| id | doaj.art-f57dff4339e143c28eecea7aa70101d0 |
| institution | Directory Open Access Journal |
| issn | 1868-7083 |
| language | English |
| last_indexed | 2024-03-07T14:55:59Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Clinical Epigenetics |
| spelling | doaj.art-f57dff4339e143c28eecea7aa70101d02024-03-05T19:27:29ZengBMCClinical Epigenetics1868-70832024-01-0116111810.1186/s13148-023-01610-wMethylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescenceIvona Bečeheli0Marina Horvatiček1Maja Perić2Barbara Nikolić3Cyrielle Holuka4Marija Klasić5Marina Ivanišević6Mirta Starčević7Gernot Desoye8Dubravka Hranilović9Jonathan D. Turner10Jasminka Štefulj11Division of Molecular Biology, Ruđer Bošković InstituteDivision of Molecular Biology, Ruđer Bošković InstituteDivision of Molecular Biology, Ruđer Bošković InstituteDepartment of Biology, Faculty of Science, University of ZagrebDepartment of Infection and Immunity, Luxembourg Institute of HealthDepartment of Biology, Faculty of Science, University of ZagrebDepartment of Obstetrics and Gynecology, University Hospital Centre ZagrebDepartment of Neonatology, University Hospital Centre ZagrebDepartment of Obstetrics and Gynecology, Medical University of GrazDepartment of Biology, Faculty of Science, University of ZagrebDepartment of Infection and Immunity, Luxembourg Institute of HealthDivision of Molecular Biology, Ruđer Bošković InstituteAbstract Background Serotonin (5-hydroxytryptamine, 5-HT) signaling is involved in neurodevelopment, mood regulation, energy metabolism, and other physiological processes. DNA methylation plays a significant role in modulating the expression of genes responsible for maintaining 5-HT balance, such as 5-HT transporter (SLC6A4), monoamine oxidase A (MAOA), and 5-HT receptor type 2A (HTR2A). Maternal metabolic health can influence long-term outcomes in offspring, with DNA methylation mediating these effects. We investigated associations between maternal metabolic parameters—pre-pregnancy body mass index (pBMI), gestational weight gain (GWG), and glucose tolerance status (GTS), i.e., gestational diabetes mellitus (GDM) versus normal glucose tolerance (NGT)—and cord blood methylation of SLC6A4, MAOA, and HTR2A in participants from our PlaNS birth cohort. CpG sites (15, 9, and 2 in each gene, respectively) were selected based on literature and in silico data. Methylation levels were quantified by bisulfite pyrosequencing. We also examined the stability of methylation patterns in these genes in circulating blood cells from birth to adolescence using longitudinal DNA methylation data from the ARIES database. Results None of the 203 PlaNS mothers included in this study had preexisting diabetes, 99 were diagnosed with GDM, and 104 had NGT; all neonates were born at full term by planned Cesarean section. Methylation at most CpG sites differed between male and female newborns. SLC6A4 methylation correlated inversely with maternal pBMI and GWG, while methylation at HTR2A site -1665 correlated positively with GWG. None of the maternal metabolic parameters statistically associated with MAOA methylation. DNA methylation data in cord blood and peripheral blood at ages 7 and 15 years were available for 808 participants from the ARIES database; 4 CpG sites (2 in SLC6A4 and 2 in HTR2A) overlapped between the PlaNS and ARIES cohorts. A positive correlation between methylation levels in cord blood and peripheral blood at 7 and 15 years of age was observed for both SLC6A4 and HTR2A CpG sites. Conclusions Methylation of 5-HT regulating genes in cord blood cells is influenced by neonatal sex, with maternal metabolism playing an additional role. Inter-individual variations present in circulating blood cells at birth are still pronounced in childhood and adolescence.https://doi.org/10.1186/s13148-023-01610-wEarly-life adversityMaternal obesityALSPACEpigeneticDoHADSex differences |
| spellingShingle | Ivona Bečeheli Marina Horvatiček Maja Perić Barbara Nikolić Cyrielle Holuka Marija Klasić Marina Ivanišević Mirta Starčević Gernot Desoye Dubravka Hranilović Jonathan D. Turner Jasminka Štefulj Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence Clinical Epigenetics Early-life adversity Maternal obesity ALSPAC Epigenetic DoHAD Sex differences |
| title | Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence |
| title_full | Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence |
| title_fullStr | Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence |
| title_full_unstemmed | Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence |
| title_short | Methylation of serotonin regulating genes in cord blood cells: association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence |
| title_sort | methylation of serotonin regulating genes in cord blood cells association with maternal metabolic parameters and correlation with methylation in peripheral blood cells during childhood and adolescence |
| topic | Early-life adversity Maternal obesity ALSPAC Epigenetic DoHAD Sex differences |
| url | https://doi.org/10.1186/s13148-023-01610-w |
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