The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring

Soubry, Adelheid; Murphy, Susan K.; Huang, Zhiqing; Murtha, Amy P.; Schildkraut, J M; Jirtle, RL; Wang, F; Kurtzberg, Joanne; Demark‐Wahnefried, Wendy; Forman,; Hoyo, Cathrine

doi:10.1186/1868-7083-3-2

Cited by 56 publications

(57 citation statements)

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“…Previous findings show that prenatal exposure to famine15 predicts lower IGF2 DMR methylation, and that adult offspring of fathers (but not mothers) exposed prenatally to famine had higher BMIs 64. Paternal obesity65 and maternal depression/antidepressant use66 predict lower IGF2 DMR methylation, and lower IGF2 DMR methylation has been linked to lower plasma IGF and lower birth weight67 and greater childhood obesity risk,49 presumably due to rapid early growth, risk of colorectal cancer41 68 and other conditions 15 16 69 70. A speculative explanation which extends the extant literature is that black fathers’ epigenomes may embody an intergenerational legacy of nutritional/metabolic disadvantage, information that may be carried forward through the germline to subsequent generations 71 65.…”

Section: Discussionmentioning

confidence: 93%

Epigenetic regulation of Newborns’ imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status

King

Murphy

Hoyo

2015

J Epidemiol Community Health

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Background Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood. Methods We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010–2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences. Results Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education. Conclusions Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers.

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Section: Discussionmentioning

confidence: 93%

Epigenetic regulation of Newborns’ imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status

King

Murphy

Hoyo

2015

J Epidemiol Community Health

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“…Although Murphy et al (31) reported that no differences for IGF2/H19 DMR were found across cell type in cord blood, further studies are needed to confirm that DHA exposure induces DNA methylation changes regardless of blood cell subtypes. There is some evidence that DNA methylation may be altered by paternal BMI (41) or maternal use of antidepressive drugs during pregnancy (40). We did not collect any information on paternal BMI or maternal use of drugs during pregnancy.…”

Section: Discussionmentioning

confidence: 99%

Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

Lee

Barraza‐Villarreal

Biessy³

et al. 2014

Physiological Genomics

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I. Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants. Physiol Genomics 46: 851-857, 2014. First published October 7, 2014 doi:10.1152/physiolgenomics.00061.2014.-Epigenetic regulation of imprinted genes is regarded as a highly plausible explanation for linking dietary exposures in early life with the onset of diseases during childhood and adulthood. We sought to test whether prenatal dietary supplementation with docosahexaenoic acid (DHA) during pregnancy may modulate epigenetic states at birth. This study was based on a randomized intervention trial conducted in Mexican pregnant women supplemented daily with 400 mg of DHA or a placebo from gestation week 18 -22 to parturition. We applied quantitative profiling of DNA methylation states at IGF2 promoter 3 (IGF2 P3), IGF2 differentially methylated region (DMR), and H19 DMR in cord blood mononuclear cells of the DHA-supplemented group (n ϭ 131) and the control group (n ϭ 130). In stratified analyses, DNA methylation levels in IGF2 P3 were significantly higher in the DHA group than the control group in preterm infants (P ϭ 0.04). We also observed a positive association between DNA methylation levels and maternal body mass index; IGF2 DMR methylation was higher in the DHA group than the control group in infants of overweight mothers (P ϭ 0.03). In addition, at H19 DMR, methylation levels were significantly lower in the DHA group than the control group in infants of normal weight mothers (P ϭ 0.01). Finally, methylation levels at IGF2/H19 imprinted regions were associated with maternal BMI. These findings suggest that epigenetic mechanisms may be modulated by DHA, with potential impacts on child growth and development. epigenetics; DHA supplementation; pregnancy; imprinted genes; maternal BMI; IGF2; H19 EPIGENETIC MODIFICATIONS ARE thought to stabilize gene expression patterns in specific cell types and to play a role in the maintenance of cell identity and differentiation fates. However, epigenetic patterns are globally reconfigured when gametes fuse to form the zygote, and gamete precursors develop and migrate in the embryo (50). Epigenetic reprogramming occurs during normal embryonic and fetal development and differentiation and might be affected by environmental exposures, resulting in long-lasting changes that could affect health and the risk of diseases in later life (2). The critical window of vulnerability to relevant environmental exposures during epigenetic reprogramming is crucial to understand the full impact of these factors on health (7). Environmental exposures that affect epigenetic reprogramming and maintenance of cell identity have been documented, including in utero exposure to dietary micronutrients (31, 43), caloric restriction (10), protein restriction (8), and cigarette smoking (30). Therefore, epigenetic regulation is regarded as a highly plausible explanation for linking dietary exposures in utero and in early life with the onset of chronic dise...

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“…24 We chose the nine imprinted marks in this study because these DMRs regulate genes already known to be important to appropriate growth and development, 25, 26 neurological function 27 and to social and maternal nurturing behaviors (from studies in mice) 25 (for review, see Murphy et al 28 ). In addition, our previous studies have shown that these regions exhibit differential malleability in methylation profiles in response to antidepressant use during pregnancy, 29 maternal depression, 30 smoking, 31 folic acid intake 26 and paternal obesity. 32 To our knowledge, no studies have provided mechanistic insights into the association between antibiotic intake during pregnancy and birth weight, although epigenetic mechanisms have been hypothesized.…”

Section: Introductionmentioning

confidence: 97%

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring

et al. 2013

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Objectives:Low birth weight (LBW) has been associated with common adult-onset chronic diseases, including obesity, cardiovascular disease, type II diabetes and some cancers. The etiology of LBW is multi-factorial. However, recent evidence suggests exposure to antibiotics may also increase the risk of LBW. The mechanisms underlying this association are unknown, although epigenetic mechanisms are hypothesized. In this study, we evaluated the association between maternal antibiotic use and LBW and examined the potential role of altered DNA methylation that controls growth regulatory imprinted genes in these associations.Methods:Between 2009–2011, 397 pregnant women were enrolled and followed until delivery. Prenatal antibiotic use was ascertained through maternal self-report. Imprinted genes methylation levels were measured at differentially methylated regions (DMRs) using bisulfite pyrosequencing. Generalized linear models were used to examine associations among antibiotic use, birth weight and DMR methylation fractions.Results:After adjusting for infant gender, race/ethnicity, maternal body mass index, delivery route, gestational weight gain, gestational age at delivery, folic acid intake, physical activity, maternal smoking and parity, antibiotic use during pregnancy was associated with 138 g lower birth weight compared with non-antibiotic use (β-coefficient=−132.99, s.e.=50.70, P=0.008). These associations were strongest in newborns of women who reported antibiotic use other than penicillins (β-coefficient=−135.57, s.e.=57.38, P=0.02). Methylation at five DMRs, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) and PEG3 (P=0.08), was associated with maternal antibiotic use; among these, only methylation at the PLAGL1 DMR was also associated with birth weight.Conclusion:We report an inverse association between in utero exposure to antibiotics and lower infant birth weight and provide the first empirical evidence supporting imprinted gene plasticity in these associations.

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The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring

Cited by 56 publications

References 56 publications

Epigenetic regulation of Newborns’ imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status

Epigenetic regulation of Newborns’ imprinted genes related to gestational growth: patterning by parental race/ethnicity and maternal socioeconomic status

Dietary supplementation with polyunsaturated fatty acid during pregnancy modulates DNA methylation at IGF2/H19 imprinted genes and growth of infants

Associations between antibiotic exposure during pregnancy, birth weight and aberrant methylation at imprinted genes among offspring

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