Genomic imprinting status of IGF-II and H19 in placentas of fetal growth restriction patients

Wang, Ying; Jing, Fu; Song, Wei; Wang, Li Li

doi:10.1007/s12041-010-0027-9

Cited by 13 publications

(10 citation statements)

References 18 publications

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“…Most of the research paid close attention to whether loss of imprinting of IGF-II and H19 existed in the placentas of pregnancy-related complications [13–18]. There was loss of imprinting of H19 in the placentas of fetal growth restriction [13, 17] and pre-eclampsia patients [14, 15]. There was no loss of genomic imprinting of IGF-II and H19 in placentas of diabetic pregnancies with fetal macrosomia [18].…”

Section: Discussionmentioning

confidence: 99%

“…Previous research focused on whether loss of imprinting status of IGF-II and H19 existed in the placentas of congenital growth disorders such as Beckwith-Wiedemann (BWS) [11], Silver-Russell (SRS) syndromes [12], fetal growth restriction (FGR) [13] and pre-eclampsia [14]. But there has been little research concerning the relation between the expression of IGF-II and H19 and these diseases.…”

Section: Introductionmentioning

confidence: 99%

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Maternal mRNA expression levels of H19 are inversely associated with risk of macrosomia

Jiang¹,

Yu²,

Xun³

et al. 2014

aoms

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IntroductionTo investigate the associations between the mRNA levels of H19 in term placenta and risk of macrosomia.Material and methodsTerm placentas were collected from 37 macrosomia and 37 matched neonates with normal birth weight (controls) born in Changzhou Women and Children Health Hospital, Jiangsu province, P. R. China from March 1 to June 30, 2008. The mRNA levels of H19 in those placentas were measured by real-time polymerase chain reaction (PCR). Simple and multiple logistic regression models were used to explore the risk factors in the development of macrosomia. All analyses were performed using Stata 10.0 (StataCorp, College Station, Texas, USA).ResultsThe average H19 mRNA level of the macrosomia group was 1.450 ±0.456 while in the control group it was 2.080 ±1.296. Based on the result of Student's t test, there was a significant difference in H19 mRNA level between the macrosomia group and the control group (p = 0.008). After controlling for potential confounders, the multivariable adjusted odds ratio (OR) of macrosomia for those in the highest tertile of H19 mRNA level was 0.12 (95% CI: 0.02–0.59) when compared to those in the lowest tertile (p for linear trend = 0.009).ConclusionsThe term placental H19 mRNA levels were inversely related to the occurrence of macrosomia. Our findings suggest that the low expression of H19 mRNA may contribute to the development of macrosomia.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Maternal mRNA expression levels of H19 are inversely associated with risk of macrosomia

Jiang¹,

Yu²,

Xun³

et al. 2014

aoms

View full text Add to dashboard Cite

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“…Altered H19 and IGF2 expression have been linked to foetal growth restriction and small for gestational age (SGA) in humans [ 26 , 77 ]. A partial loss of imprinting (LOI), together with biallelic expression of H19 , were detected in placentas from SGA and PE pregnancies [ 26 , 73 , 76 ].…”

Section: H19mentioning

confidence: 99%

“…This association indirectly provides evidence that there may be a loss of imprinting at the H19/IGF2 locus in placentas from assisted reproductive technology (ART) pregnancies [ 78 , 79 ] which a meta-analysis has recently shown are more likely to be affected by a wide range of pregnancy complications [ 80 ]. Currently there are conflicting reports as to the effect of altered H19/IGF2 expression on birth weight, with four studies finding an association [ 26 , 77 , 81 , 82 ], while three different studies did not observe this association with placentas from ART pregnancies [ 78 , 79 , 83 ]. Increased 5-hydroxymethlycytosine (5hmC) methylation within the H19 gene body is positively associated with birth weight, but there is no such association between 5hmC methylation and H19 gene expression [ 84 ].…”

Section: H19mentioning

confidence: 99%

Mechanistic Insight into Long Noncoding RNAs and the Placenta

McAninch

Roberts

Bianco‐Miotto

2017

IJMS

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Long non-coding RNAs (lncRNAs) are classified as RNAs greater than 200 nucleotides in length that do not produce a protein product. lncRNAs are expressed with cellular and temporal specificity and have been shown to play a role in many cellular events, including the regulation of gene expression, post-transcriptional modifications and epigenetic modifications. Since lncRNAs were first discovered, there has been increasing evidence that they play important roles in the development and function of most organs, including the placenta. The placenta is an essential transient organ that facilitates communication and nutrient exchange between the mother and foetus. The placenta is of foetal origin and begins to form shortly after the embryo implants into the uterine wall. The placenta relies heavily on the successful differentiation and function of trophoblast cells, including invasion as well as the formation of the maternal/foetal interface. Here, we review the current literature surrounding the involvement of lncRNAs in the development and function of trophoblasts and the human placenta.

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“…Although the symptoms of these conditions manifest late in pregnancy, their pathogenesis is commonly attributed to compromised first trimester placental development [44]. Previous research on genomic imprinting in the human placenta has focused on the term placenta [25], [32], [36], [41], [45], [46] and data during the first trimester of gestation is limited [27], [34], [35], [47]. In the present study, we investigated the imprinting status (i.e., allele-specific expression) of three genes, H19 , IGF2 and IGF2R , which have known, but poorly understood, associations with pregnancy complications and placental abnormalities in humans and/or animal models [6], [7], [8], [9], [10].…”

Section: Discussionmentioning

confidence: 99%

Quantitative Allele-Specific Expression and DNA Methylation Analysis of H19, IGF2 and IGF2R in the Human Placenta across Gestation Reveals H19 Imprinting Plasticity

et al. 2012

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Imprinted genes play important roles in placental differentiation, growth and function, with profound effects on fetal development. In humans, H19 and IGF2 are imprinted, but imprinting of IGF2R remains controversial. The H19 non-coding RNA is a negative regulator of placental growth and altered placental imprinting of H19-IGF2 has been associated with pregnancy complications such as preeclampsia, which have been attributed to abnormal first trimester placentation. This suggests that changes in imprinting during the first trimester may precede aberrant placental morphogenesis. To better understand imprinting in the human placenta during early gestation, we quantified allele-specific expression for H19, IGF2 and IGF2R in first trimester (6–12 weeks gestation) and term placentae (37–42 weeks gestation) using pyrosequencing. Expression of IGF2R was biallelic, with a mean expression ratio of 49∶51 (SD = 0.07), making transient imprinting unlikely. Expression from the repressed H19 alleles ranged from 1–25% and was higher (P<0.001) in first trimester (13.5±8.2%) compared to term (3.4±2.1%) placentae. Surprisingly, despite the known co-regulation of H19 and IGF2, little variation in expression of the repressed IGF2 alleles was observed (2.7±2.0%). To identify regulatory regions that may be responsible for variation in H19 allelic expression, we quantified DNA methylation in the H19-IGF2 imprinting control region and H19 transcription start site (TSS). Unexpectedly, we found positive correlations (P<0.01) between DNA methylation levels and expression of the repressed H19 allele at 5 CpG’s 2000 bp upstream of the H19 TSS. Additionally, DNA methylation was significantly higher (P<0.05) in first trimester compared with term placentae at 5 CpG’s 39–523 bp upstream of the TSS, but was not correlated with H19 repressed allele expression. Our data suggest that variation in H19 imprinting may contribute to early programming of placental phenotype and illustrate the need for quantitative and robust methodologies to further elucidate the role of imprinted genes in normal and pathological placental development.

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Genomic imprinting status of IGF-II and H19 in placentas of fetal growth restriction patients

Cited by 13 publications

References 18 publications

Maternal mRNA expression levels of H19 are inversely associated with risk of macrosomia

Maternal mRNA expression levels of H19 are inversely associated with risk of macrosomia

Mechanistic Insight into Long Noncoding RNAs and the Placenta

Quantitative Allele-Specific Expression and DNA Methylation Analysis of H19, IGF2 and IGF2R in the Human Placenta across Gestation Reveals H19 Imprinting Plasticity

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