Dataset Information

Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

ABSTRACT: BACKGROUND:Imprinted genes are a unique subset of few genes that have been differentially methylated region (DMR) in a parental origin-dependent manner during gametogenesis, and these genes are highly protected during pre-implantation epigenetic reprogramming. Several studies have shown that the particular vulnerability of imprinting genes during suboptimal pre- and peri-conception micro-environments often is occurred by assisted reproduction techniques (ART). This study investigated the methylation status of H19/IGF2 DMR at high-quality expanding/expanded human blastocysts donated by healthy individuals to evaluate the risks linked to ART. METHODS:Methylation levels of H19/IGF2 DMR were analyzed by bisulfite conversion and sequencing at 18 CpG sites (CpGs) located in this region. RESULTS:The overall percentage of methylated CpGs and the proportion of hyper-methylated clones of H19/IGF2 DMR in analyzed blastocysts were 37.85±4.87% and 43.75±5.1%, respectively. For validation of our technique, the corresponding methylation levels of peripheral human lymphocytes were defined (49.52±1.86% and 50%, respectively). CONCLUSIONS:Considering the absence of in vivo- produced human embryos, it is not possible to conclude that the methylation found in H19/IGF2 DMR is actually normal or abnormal. Regarding the possible risks associated with ART, the procedures should be optimized in order to at least reduce some of the epigenetic risks.

SUBMITTER: Derakhshan-Horeh M

PROVIDER: S-EPMC5141249 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

Derakhshan-Horeh Marzieh M Abolhassani Farid F Jafarpour Farnoosh F Moini Ashraf A Karbalaie Khadijeh K Hosseini Sayyed Morteza SM Ostadhosseini Somayyeh S Nasr-Esfahani Mohammad Hossein MH

Iranian biomedical journal 20160507 1

<h4>Background</h4>Imprinted genes are a unique subset of few genes that have been differentially methylated region (DMR) in a parental origin-dependent manner during gametogenesis, and these genes are highly protected during pre-implantation epigenetic reprogramming. Several studies have shown that the particular vulnerability of imprinting genes during suboptimal pre- and peri-conception micro-environments often is occurred by assisted reproduction techniques (ART). This study investigated the ...[more]

PMID: 27432596

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Project description:Although a higher consumption of alcohol, which is a methyl-group antagonist, was previously associated with colorectal cancer risk, mechanisms remain poorly understood.We hypothesized that excess alcohol consumption might increase risk of colorectal carcinoma with hypomethylation of insulin-like growth factor 2 (IGF2) differentially methylated region-0 (DMR0), which was previously associated with a worse prognosis.With the use of a molecular pathologic epidemiology database in 2 prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association between alcohol intake and incident colorectal cancer according to the tumor methylation level of IGF2 DMR0. Duplication-method Cox proportional cause-specific hazards regression for competing risk data were used to compute HRs and 95% CIs. In addition, we investigated intakes of vitamin B-6, vitamin B-12, methionine, and folate as exposures.During 3,206,985 person-years of follow-up, we identified 993 rectal and colon cancer cases with an available tumor DNA methylation status. Compared with no alcohol consumption, the consumption of ?15 g alcohol/d was associated with elevated risk of colorectal cancer with lower levels of IGF2 DMR0 methylation [within the first and second quartiles: HRs of 1.55 (95% CI: 1.08, 2.24) and 2.11 (95% CI: 1.44, 3.07), respectively]. By contrast, alcohol consumption was not associated with cancer with higher levels of IGF2 DMR0 methylation. The association between alcohol and cancer risk differed significantly by IGF2 DMR0 methylation level (P-heterogeneity = 0.006). The association of vitamin B-6, vitamin B-12, and folate intakes with cancer risk did not significantly differ according to IGF2 DMR0 methylation level (P-heterogeneity > 0.2).Higher alcohol consumption was associated with risk of colorectal cancer with IGF2 DMR0 hypomethylation but not risk of cancer with high-level IGF2 DMR0 methylation. The association between alcohol intake and colorectal cancer risk may differ by tumor epigenetic features.

Project description:DNA methylation disturbance is associated with defective human sperm. However, oligozoospermia (OZ) and asthenozoospermia (AZ) usually present together, and the relationship between the single-phenotype defects in human sperm and DNA methylation is poorly understood. In this study, 20 infertile OZ patients and 20 infertile AZ patients were compared with 20 fertile normozoospermic men. Bisulfate-specific PCR was used to analyze DNA methylation of the H19-DMR and the DAZL promoter in these subjects. A similar DNA methylation pattern of the H19-DMR was detected in AZ and NZ(control), with only complete methylation and mild hypomethylation(<50% unmethylated CpGs) identified, and there was no significant difference in the occurrence of these two methylation patterns between AZ and NZ (P>0.05). However, the methylation pattern of severe hypomethylation (>50% unmethylated CpGs ) and complete unmethylation was only detected in 5 OZ patients, and the occurrence of these two methylation patterns was 8.54±10.86% and 9±6.06%, respectively. Loss of DNA methylation of the H19-DMR in the OZ patients was found to mainly occur in CTCF-binding site 6, with occurrence of 18.15±14.71%, which was much higher than that in patients with NZ (0.84±2.05%) and AZ (0.58±1.77%) (P<0.001).Additional, our data indicated the occurrence of >20% methylated clones in the DAZL promoter only in infertile patients, there was no significant difference between the AZ and OZ patients in the proportion of moderately-to-severely hypermethylated clones (p>0.05). In all cases, global sperm genome methylation analyses, using LINE1 transposon as the indicator, showed that dysregulation of DNA methylation is specifically associated with the H19-DMR and DAZL promoter. Therefore, abnormal DNA methylation status of H19-DMR, especially at the CTCF-binding site 6, is closely associated with OZ. Abnormal DNA methylation of the DAZL promoter might represent an epigenetic marker of male infertility.

Project description:UnlabelledBackgroundThe insulin-like growth factor 2 (IGF2) and H19 imprinted genes control growth and body composition. Adverse in-utero environments have been associated with obesity-related diseases and linked with altered DNA methylation at the IGF2/H19 locus. Postnatally, methylation at the IGF2/H19 imprinting control region (ICR) has been linked with cerebellum weight. We aimed to investigate whether decreased IGF2/H19 ICR methylation is associated with decreased birth and childhood anthropometry and increased contemporaneous adiposity.DNA methylation in peripheral blood (n = 315) at 17 years old was measured at 12 cytosine-phosphate-guanine sites (CpGs), analysed as Sequenom MassARRAY EpiTYPER units within the IGF2/H19 ICR. Birth size, childhood head circumference (HC) at six time-points and anthropometry at age 17 years were measured. DNA methylation was investigated for its association with anthropometry using linear regression.ResultsThe principal component of IGF2/H19 ICR DNA methylation (representing mean methylation across all CpG units) positively correlated with skin fold thickness (at four CpG units) (P-values between 0.04 to 0.001) and subcutaneous adiposity (P = 0.023) at age 17, but not with weight, height, BMI, waist circumference or visceral adiposity. IGF2/H19 methylation did not associate with birth weight, length or HC, but CpG unit 13 to 14 methylation was negatively associated with HC between 1 and 10 years. ?-coefficients of four out of five remaining CpG units also estimated lower methylation with increasing childhood HC.ConclusionsAs greater IGF2/H19 methylation was associated with greater subcutaneous fat measures, but not overall, visceral or central adiposity, we hypothesize that obesogenic pressures in youth result in excess fat being preferentially stored in peripheral fat depots via the IGF2/H19 domain. Secondly, as IGF2/H19 methylation was not associated with birth size but negatively with early childhood HC, we hypothesize that the HC may be a more sensitive marker of early life programming of the IGF axis and of fetal physiology than birth size. To verify this, investigations of the dynamics of IGF2/H19 methylation and expression from birth to adolescence are required.

Dataset Information

Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

Publications

Methylation Status of H19/IGF2 Differentially Methylated Region in in vitro Human Blastocysts Donated by Healthy Couples

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