Isma'il Kadam, Mudar Dalloul, Jeanette Hausser, Monique Huntley, Lori Hoepner, Lawrence Fordjour, Joan Hittelman, Anjana Saxena, Jia Liu, Itamar D Futterman, Howard Minkoff, Xinyin Jiang
{"title":"有或无妊娠期糖尿病的孕妇单碳代谢营养素与胎儿DNA甲基化之间的关系","authors":"Isma'il Kadam, Mudar Dalloul, Jeanette Hausser, Monique Huntley, Lori Hoepner, Lawrence Fordjour, Joan Hittelman, Anjana Saxena, Jia Liu, Itamar D Futterman, Howard Minkoff, Xinyin Jiang","doi":"10.1186/s13148-023-01554-1","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B<sub>12</sub>, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM.</p><p><strong>Results: </strong>In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25-33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = - 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = - 0.13, p = 0.049 and r = - 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = - 0.28, p = 0.015).</p><p><strong>Conclusions: </strong>In conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.</p>","PeriodicalId":48652,"journal":{"name":"Clinical Epigenetics","volume":null,"pages":null},"PeriodicalIF":5.7000,"publicationDate":"2023-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10464204/pdf/","citationCount":"2","resultStr":"{\"title\":\"Associations between nutrients in one-carbon metabolism and fetal DNA methylation in pregnancies with or without gestational diabetes mellitus.\",\"authors\":\"Isma'il Kadam, Mudar Dalloul, Jeanette Hausser, Monique Huntley, Lori Hoepner, Lawrence Fordjour, Joan Hittelman, Anjana Saxena, Jia Liu, Itamar D Futterman, Howard Minkoff, Xinyin Jiang\",\"doi\":\"10.1186/s13148-023-01554-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B<sub>12</sub>, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM.</p><p><strong>Results: </strong>In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25-33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = - 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = - 0.13, p = 0.049 and r = - 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. 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引用次数: 2
摘要
背景:妊娠期糖尿病(GDM)以妊娠期高血糖为特征,增加了胎儿巨大儿、儿童肥胖和生命后期心脏代谢紊乱的风险。这一过程部分归因于生长和应激相关途径中的DNA甲基化修饰。参与单碳代谢(OCM)的营养素,如叶酸、胆碱、甜菜碱和维生素B12,为这些途径的DNA甲基化提供甲基。因此,本研究旨在确定母亲OCM营养摄入和水平是否会改变胎儿DNA甲基化,进而改变妊娠期和非妊娠期GDM胎儿的生长模式。结果:在2016年9月至2019年6月在一所学术机构进行的这项前瞻性研究中,我们招募了76名25-33周孕龄的有或无GDM的孕妇,通过饮食回顾评估她们的OCM营养摄入量,并测量了母体血液OCM营养水平。我们还收集了分娩时的胎盘和脐带血样本,以检测胎儿组织中改变胎儿生长和应激反应的基因(如胰岛素样生长因子2 (IGF2)和促肾上腺皮质激素释放激素(CRH))的DNA甲基化。我们使用广义线性混合模型分析了母体OCM营养素与胎儿DNA甲基化之间的关系。我们的研究结果表明,母亲胆碱摄入量与GDM和非GDM妊娠的脐带血CRH甲基化水平呈正相关(r = 0.13, p = 0.007)。此外,CRH调节的下游应激激素皮质醇与母体胆碱摄入量呈负相关(r = - 0.36, p = 0.021)。在妊娠期糖尿病和非妊娠期糖尿病孕妇中,较高的母亲甜菜碱摄入量和血清叶酸水平与较低的脐带血和胎盘IGF2 DNA甲基化相关(r = - 0.13, p = 0.049和r = - 0.065, p = 0.034)。此外,母亲甜菜碱摄入量与婴儿出生体重呈负相关(r = - 0.28, p = 0.015)。结论:总之,我们观察到无论GDM状态如何,母体OCM营养素与胎儿DNA甲基化水平之间存在复杂的相互关系,这可能在表观遗传学上编程了与胎儿生长和应激反应相关的分子途径。
Associations between nutrients in one-carbon metabolism and fetal DNA methylation in pregnancies with or without gestational diabetes mellitus.
Background: Gestational diabetes mellitus (GDM), characterized by hyperglycemia that develops during pregnancy, increases the risk of fetal macrosomia, childhood obesity and cardiometabolic disorders later in life. This process has been attributed partly to DNA methylation modifications in growth and stress-related pathways. Nutrients involved with one-carbon metabolism (OCM), such as folate, choline, betaine, and vitamin B12, provide methyl groups for DNA methylation of these pathways. Therefore, this study aimed to determine whether maternal OCM nutrient intakes and levels modified fetal DNA methylation and in turn altered fetal growth patterns in pregnancies with and without GDM.
Results: In this prospective study at a single academic institution from September 2016 to June 2019, we recruited 76 pregnant women with and without GDM at 25-33 weeks gestational age and assessed their OCM nutrient intake by diet recalls and measured maternal blood OCM nutrient levels. We also collected placenta and cord blood samples at delivery to examine fetal tissue DNA methylation of the genes that modify fetal growth and stress response such as insulin-like growth factor 2 (IGF2) and corticotropin-releasing hormone (CRH). We analyzed the association between maternal OCM nutrients and fetal DNA methylation using a generalized linear mixed model. Our results demonstrated that maternal choline intake was positively correlated with cord blood CRH methylation levels in both GDM and non-GDM pregnancies (r = 0.13, p = 0.007). Further, the downstream stress hormone cortisol regulated by CRH was inversely associated with maternal choline intake (r = - 0.36, p = 0.021). Higher maternal betaine intake and serum folate levels were associated with lower cord blood and placental IGF2 DNA methylation (r = - 0.13, p = 0.049 and r = - 0.065, p = 0.034, respectively) in both GDM and non-GDM pregnancies. Further, there was an inverse association between maternal betaine intake and birthweight of infants (r = - 0.28, p = 0.015).
Conclusions: In conclusion, we observed a complex interrelationship between maternal OCM nutrients and fetal DNA methylation levels regardless of GDM status, which may, epigenetically, program molecular pathways related to fetal growth and stress response.
Clinical EpigeneticsBiochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍:
Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.