DNA Methylation Trajectories During Pregnancy

Gruzieva, Olena; Merid, Simon Kebede; Chen, Su; Mukherjee, Nandini; Hedman, Anna M.; Almqvist, Catarina; Andolf, Ellika; Jiang, Yu; Kere, Juha; Scheynius, Annika; Söderhäll, Cilla; Ullemar, Vilhelmina; Karmaus, Wilfried; Melén, Erik; Arshad, Syed Hasan; Pershagen, Göran

doi:10.1177/2516865719867090

Cited by 35 publications

(45 citation statements)

References 45 publications

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“…These hormone fluctuations are associated with immune function and susceptibility to certain inflammatory diseases. Several studies have performed epigenetic and transcriptional profiling at different stages of life: i) ( 122 ), ii) ( 123 ), iii) ( 124 ), iv) ( 125 ), v) ( 126 ), vi) ( 127 ), vii) ( 128 ), and viii) ( 129 ).…”

Section: Immunological Transcriptome and Epigenome Differences Durimentioning

confidence: 99%

“…In light of the phenotypic and functional changes to maternal immune cells, several studies have also investigated the blood transcriptome ( 125 , 126 , 167 ), epigenome ( 124 , 127 ) and proteome ( 168 ) across pregnancy. Longitudinal transcriptome analysis of whole blood in healthy pregnancy revealed sustained downregulation of interferon response and plasma cell signatures, and sustained upregulation of neutrophil and erythropoiesis signatures, with changes observable at less than 16 weeks’ gestation ( 126 ).…”

Section: Immunological Transcriptome and Epigenome Differences Durimentioning

confidence: 99%

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Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics

et al. 2021

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Sexual dimorphism refers to differences between biological sexes that extend beyond sexual characteristics. In humans, sexual dimorphism in the immune response has been well demonstrated, with females exhibiting lower infection rates than males for a variety of bacterial, viral, and parasitic pathogens. There is also a substantially increased incidence of autoimmune disease in females compared to males. Together, these trends indicate that females have a heightened immune reactogenicity to both self and non-self-molecular patterns. However, the molecular mechanisms driving the sexually dimorphic immune response are not fully understood. The female sex hormones estrogen and progesterone, as well as the male androgens, such as testosterone, elicit direct effects on the function and inflammatory capacity of immune cells. Several studies have identified a sex-specific transcriptome and methylome, independent of the well-described phenomenon of X-chromosome inactivation, suggesting that sexual dimorphism also occurs at the epigenetic level. Moreover, distinct alterations to the transcriptome and epigenetic landscape occur in synchrony with periods of hormonal change, such as puberty, pregnancy, menopause, and exogenous hormone therapy. These changes are also mirrored by changes in immune cell function. This review will outline the evidence for sex hormones and pregnancy-associated hormones as drivers of epigenetic change, and how this may contribute to the sexual dimorphism. Determining the effects of sex hormones on innate immune function is important for understanding sexually dimorphic autoimmune diseases, sex-specific responses to pathogens and vaccines, and how innate immunity is altered during periods of hormonal change (endogenous or exogenous).

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Section: Immunological Transcriptome and Epigenome Differences Durimentioning

confidence: 99%

Section: Immunological Transcriptome and Epigenome Differences Durimentioning

confidence: 99%

Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics

et al. 2021

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“…This response could have been associated with the transfer of methyl groups from the ewe to the fetus. In humans, it has been reported that the increase in dietary methyl donors consumed alters the trajectories of DNA methylation during pregnancy [38]. The increase in the percentages of 5-hmC in the lambs born to dams with supplementation during the second third of gestation could have been associated with the amounts of dietary methyl groups and could have affected organ development (brain and liver) and increased the hereditable capacity of 5-hmC in whole blood [39].…”

Section: Discussionmentioning

confidence: 99%

Supplemental Herbal Choline Increases 5-hmC DNA on Whole Blood from Pregnant Ewes and Offspring

Roque-Jiménez

Mendoza-Martínez

Vazquez-Valladolid

et al. 2020

Animals

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Herbal formulas during pregnancy have been used in developing countries. Despite that, the potential effects on the mother and offspring and whether those supplements elicit epigenetic modifications is still unknown. Therefore, our objectives were to determine the effects of supplemental herbal choline source (BCho) on the percentage of 5-hmC in whole blood from gestating ewes and their offspring, as well as determining the milk quality and growth of the offspring. Thirty-five gestating Rambouillet ewes were randomly assigned to five treatments: T1, supplementation of 4 g per day (gd−1) of BCho during the first third of gestation; T2, supplementation of 4 gd−1 of BCho during the second third of gestation; T3, supplementation of 4 gd−1 of BCho during the last third of gestation; T4, supplementation of 4 gd−1 of BCho throughout gestation; and T5, no BCho supplementation (control). For the 5-hmC DNA analysis, whole blood from ewes was sampled before pregnancy and at each third of gestation (50 days). Whole blood from lambs was sampled five weeks after birth. The evaluation of the nutritional programming effects was conducted through the percentages of 5-hmC in the lambs. Compared with other treatments, the whole blood from ewes supplemented during T1 and T4 had the greatest 5-hmC percentages (p < 0.05). However, only ewes fed BCho throughout gestation (T4) maintained the greatest percentages of 5-hmC (p < 0.05). The lamb growth performance indicated that the BCho maternal supplementation did not affect the nutritional programming. However, the lambs born from ewes supplemented during T2 had the greatest 5-hmC percentages (p < 0.05). Our data suggest that ewes supplemented during T4 with BCho increase and maintain the percentages of 5-hmC in whole blood, and the offspring born from ewes supplemented with BCho during T2 maintained the greatest percentages of 5-hmC 35 d after they were born.

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“…It is known that the epigenome has a great plasticity and undergoes physiological and disease-associated alterations in response to internal and external stimuli [ 11 , 12 ]. Although studies on DNA methylation dynamics evaluating intraindividual longitudinal changes in DNA methylation are scarce, there is emerging evidence that an individual’s DNA methylation profile is subject to change on both a short- (hours to days) and long-term (months to years) timescale [ 13 , 14 ]. For the majority of the CpG-sites investigated in the present study, the largest changes in DNA methylation status occurred within the first 3 days after PICU admission, whereas any further changes beyond day 3 progressed at a slower rate.…”

Section: Discussionmentioning

confidence: 99%

Time course of altered DNA methylation evoked by critical illness and by early administration of parenteral nutrition in the paediatric ICU

et al. 2020

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Background A genome-wide study identified de novo DNA methylation alterations in leukocytes of children at paediatric intensive care unit (PICU) discharge, offering a biological basis for their impaired long-term development. Early parenteral nutrition (early-PN) in PICU, compared with omitting PN in the first week (late-PN), explained differential methylation of 23% of the affected CpG-sites. We documented the time course of altered DNA methylation in PICU and the impact hereon of early nutritional management. Results We selected 36 early-PN and 36 late-PN matched patients, and 42 matched healthy children. We quantified DNA methylation on days 3, 5 and 7 for the 147 CpG-sites of which methylation was normal upon PICU admission in this subset and altered by critical illness at PICU discharge. Methylation in patients differed from healthy children for 64.6% of the 147 CpG-sites on day 3, for 72.8% on day 5 and for 90.5% on day 7 as revealed by ANOVA at each time point. Within-patients methylation time course analyses for each CpG-site identified different patterns based on paired t test p value and direction of change. Rapid demethylation from admission to day 3 occurred for 76.2% of the CpG-sites, of which 67.9% remained equally demethylated or partially remethylated and 32.1% further demethylated beyond day 3. From admission to day 3, 19.7% of the CpG-sites became hypermethylated, of which, beyond day 3, 34.5% remained equally hypermethylated or partially demethylated again and 65.5% further hypermethylated. For 4.1% of the CpG-sites, changes only appeared beyond day 3. Finally, for the CpG-sites affected by early-PN on the last PICU day, earlier changes in DNA methylation were compared for early-PN and late-PN patients, revealing that 38.9% were already differentially methylated by day 3, another 25.0% by day 5 and another 13.9% by day 7. Conclusions Critical illness- and early-PN-induced changes in DNA methylation occurred mainly within 3 days. Most abnormalities were at least partially maintained or got worse with longer time in PICU. Interventions targeting aberrant DNA methylation changes should be initiated early.

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DNA Methylation Trajectories During Pregnancy

Cited by 35 publications

References 45 publications

Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics

Sexual Dimorphism in Innate Immunity: The Role of Sex Hormones and Epigenetics

Supplemental Herbal Choline Increases 5-hmC DNA on Whole Blood from Pregnant Ewes and Offspring

Time course of altered DNA methylation evoked by critical illness and by early administration of parenteral nutrition in the paediatric ICU

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