The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans

Prats‐Puig, Anna; Carreras‐Badosa, Gemma; Bassols, Judit; Cavelier, Patricia; Magret, Agnés; Sabench, Cristina; Zegher, Francis de; Ibáñez, Lourdes; Feil, Robert; López‐Bermejo, Abel

doi:10.1016/j.ajog.2017.05.002

Cited by 26 publications

(16 citation statements)

References 48 publications

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“…Similarly, placental DNA methylation at the IGF2-H19, GNAS and DLK1-DIO3 imprinted loci has been linked to pre and postnatal growth characteristics. 16,18,19 Moreover, our results link placental C19MC ICR methylation to the body composition of the offspring in childhood. Interestingly, maternal obesity has been suggested to alter adipocyte commitment and differentiation in the offspring via an epigenetic mechanism as well.…”

Section: Placental C19mc Icr Methylation Levels and Gene Expressionsupporting

confidence: 53%

“…14,15 Nongenetic variation or pathological disruption of DNA methylation marks in several imprinted loci, including IGF2-H19, GNAS or DLK1-DIO3, have been consistently related to changes in pre-and postnatal growth as well. [16][17][18][19] Currently, there are no reports of parental factors related to placental C19MC methylation variation, nor about the impact of C19MC differential methylation on the offspring's development. Here, we examined for the first time the placental C19MC DNA methylation levels and their association with 1) parental weight and height, 2) parental transmission of haplotypes within a SNP (rs55765443) in C19MC, 3) postnatal growth and body composition of the offspring at birth and in childhood, and 4) gene expression levels of representative C19MC miRNAs.…”

Section: Introductionmentioning

confidence: 99%

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Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

et al. 2019

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Objectives: To study DNA methylation at the C19MC locus in the placenta and its association with: 1) parental body size, 2) transmission of haplotypes for the C19MC rs55765443 SNP, 3) offspring's body size and/or body composition at birth and in childhood. Subjects and methods: Seventy-two pregnant women-infant pairs and 63 fathers were included in the study. Weight and height of mothers, fathers and newborns were registered during pregnancy or at birth (n=72). Placental DNA methylation at the C19MC imprinting control region (ICR) was quantified by bisulfite pyrosequencing. Genotyping of the SNP was performed using restriction fragment length polymorphisms. The children's body size and composition were reassessed at age 6 years (n=32). Results: Lower levels of placental C19MC methylation were associated with increased body size of the mother, specifically with higher pre-gestational and pre-delivery weights and height (β from-0.294 to-0.371; R 2 from 0.04 to 0.10 and all p<0.019), and with higher weight, height, waist and hip circumferences, and fat mass of the child (β from-0.428 to-0.552; R 2 from 0.33 to 0.56 and all p<0.009). Parental transmission of the SNP did not correlate with an altered placental methylation status at the C19MC ICR. Conclusions: Increased maternal size is associated with reduced placental C19MC methylation, which, in turn, relate to larger body size of the child.

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Section: Placental C19mc Icr Methylation Levels and Gene Expressionsupporting

confidence: 53%

Section: Introductionmentioning

confidence: 99%

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

et al. 2019

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“…11,17 Thus, we speculated that not only placental CpG1 hypomethylation but also hypermethylation at this site would result in fetal growth restriction via abnormal placental formation. It was recently reported that the placental DNA methylation pattern in RTL1 promoter regions was negatively correlated with BW gain at 1 year of age in healthy term infants, 12 suggesting that abnormal RTL1 methylation may affect future life and could be the trigger of DOHaD.…”

Section: Discussionmentioning

confidence: 99%

DNA methylation of the Rtl1 promoter in the placentas with fetal growth restriction

Fujioka

Nishida

Ashina

et al. 2019

Pediatrics & Neonatology

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Background: Small for gestational age (SGA) babies experience fetal growth restriction because of placental insufficiency, and aberrant fetal growth has been linked to DNA methylation in the placenta. An imprinted gene encoding retrotransposon-like protein 1 (RTL1) is regulated by DNA methylation in the promoter region and plays a key role in placental development. We therefore investigated the DNA methylation status of RTL1 in the placenta of infants with severe SGA. Methods: We extracted DNA from the placenta of appropriate for gestational age (AGA; gestational age 35 AE 6 weeks, birthweight 2292 AE 1006 g; n Z 12), SGA (birthweight z-score À2 SD, 33 AE 5 weeks, 1373 AE 580 g; n Z 11), and severe SGA (birthweight z-score À3 SD, 33 AE 4 weeks, 1145 g AE 423 g; n Z 7) infants, and we determined the methylation rates of five CpG sites in the CG4 (82,275,427e82,275,737 in NT_026437 sequence, NCBI database) region of the RTL1 promoter by pyrosequencing. We defined hypermethylation (>75.5%) and hypomethylation (<45.6%) based on the average methylation rate exceeding AE two standard deviations (SD) in the AGA group, respectively, and compared these among groups. Results: There was no significant difference in the average methylation of CpG1-5 (control 59%, SGA 60%, severe SGA 63%), but abnormal methylation (hyper-/hypo-methylation) in CpG1 differed significantly among the groups (control 0%, SGA 36%, severe SGA 71%). Conclusion: Infants with severe SGA have abnormal placental DNA methylation of CpG1 in the CG4 region of RTL1, suggesting the existence of disturbed epigenetic control in utero.

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“…Three key deiodinase D3 is highly expressed in the placenta for most of gestation, and placental D3 activity decreases in the 2 weeks before birth (7). The deiodinase 3 (DIO3) gene encodes D3, which is largely expressed in the placenta and is linked to prenatal growth in humans (10). According to the above, we hypothesized that changes in placental CRH and D3 may determine the time of birth and fetal growth, but we were unable to detect placental CRH and D3 during pregnancy.…”

Section: Introductionmentioning

confidence: 99%

Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

Yang

Deng

Lin

et al. 2021

Preprint

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Background Recent studies suggest that the incidence of preterm birth and SGA birth related to maternal depression, but the mechanism is unclear. The aim of this study was to explore the placental epigenetic changes involved in maternal depression induced preterm birth and small for gestational age birth. Methods Three hundred forty-five pregnant women were enrolled in this cohort study. Maternal depression in the second and third trimesters was assessed using a self-rating depression scale (SDS). We selected placental samples from pregnant women with depression and an equivalent number for samples from pregnant women without depression. Methylation of the promoter regions of the placental DIO3 and CRH genes was determined using next generation sequencing based on bisulfite sequencing PCR (NGS-BSP). Results There were 97 (28.1%) and 95 (27.5%) pregnant women who had depression in the second trimester and third trimester, respectively. The risk factors of preterm birth were older maternal age (RR = 1.43, 95%CI = 1.01–2.03), uterine infection (RR = 129.31, 95%CI = 2.16-7725.55), and maternal depression in the second trimester (RR = 79.97, 95%CI = 3.57-1792.56). The risk factors of SGA birth were low maternal BMI (RR = 0.71, 95%CI = 0.54ཞ0.92), hypertensive disorder complicating pregnancy (HDCP, RR = 4.7, 95%CI = 1.18ཞ18.72), and maternal depression in the second trimester (RR = 3.71, 95%CI = 1.31ཞ12.16). Pregnant women with depression had higher placental methylation of CRH and DIO3 genes, and there was a correlation between placental methylation of CRH and DIO3 genes. Conclusion Our study suggested that the changes in the promoter region of the placental DIO3 and CRH genes were involved in maternal depression in the second trimester induced preterm birth and small for gestational age birth.

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The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans

Cited by 26 publications

References 48 publications

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

DNA methylation of the Rtl1 promoter in the placentas with fetal growth restriction

Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

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The placental imprinted DLK1-DIO3 domain: a new link to prenatal and postnatal growth in humans

Cited by 26 publications

References 48 publications

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

Methylation of the C19MC microRNA locus in the placenta: association with maternal and chilhood body size

DNA methylation of the Rtl1 promoter in the placentas with fetal growth restriction

Promoter Methylation Changes in the Placental&nbsp;DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth

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Promoter Methylation Changes in the Placental DIO3 and CRH Genes Are Involved in the Second Trimester Maternal Depression Induced Preterm Birth and Small for Gestational Age Birth