Methylation status of imprinted genes DLK1-GTL2, MEST (PEG1), ZAC (PLAGL1), and LINE-1 elements in spermatozoa of normozoospermic men, unlike H19 imprinting control regions, is not associated with idiopathic recurrent spontaneous miscarriages

Ankolkar, Mandar; Salvi, Vinita; Warke, Himangi; Vundinti, Babu Rao; Balasinor, Nafisa

doi:10.1016/j.fertnstert.2013.01.107

Cited by 18 publications

(16 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bisulfite sequencing gave results identical to the EpiTYPER analysis, thereby validating its use in the study. Similar results were also observed in another study recently published by our group, on male partners of women undergoing idiopathic recurrent spontaneous abortions (Ankolkar et al 2013). An increase in methylation at the DMRs of several imprinted genes was observed in the resorbing embryos sired by tamoxifen-treated male rats, suggesting that the epimutations were not transmitted through sperm but could have been acquired post-fertilization.…”

Section: Discussionsupporting

confidence: 92%

Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats

et al. 2013

Self Cite

View full text Add to dashboard Cite

Genomic imprinting is an epigenetic phenomenon known to regulate fetal growth and development. Studies from our laboratory have demonstrated that treatment of adult male rats with tamoxifen increased postimplantation loss around mid gestation. Further studies demonstrated the aberrant expression of transcripts of several imprinted genes in the resorbing embryos at days 11 and 13 of gestation including IGF2. In addition, decreased methylation at the Igf2-H19 imprint control region was observed in spermatozoa and in resorbing embryos sired by tamoxifen-treated males. In this study, methylation analysis of the imprinted genes, which were found to be differentially expressed, was done using EpiTYPER in the spermatozoa of tamoxifen-treated rats and in postimplantation embryos sired by tamoxifen-treated rats. Differentially methylated regions (DMRs) for most imprinted genes have not been identified in the rats. Hence, initial experiments were performed to identify the putative DMRs in the genes selected for the study. Increased methylation at CpG islands present in the putative DMRs of a number of imprinted genes was observed in the resorbing embryos sired by tamoxifen-treated male rats. This increase in methylation is associated with the downregulation of most of these genes at the transcript level in resorbing embryos. No change in the methylation status of these genes was observed in spermatozoa. These observations suggest that a deregulation of mechanisms protecting unmethylated alleles from a wave of de novo methylation occurs following implantation. Reproduction (2013) 146 155-168

show abstract

Section: Discussionsupporting

confidence: 92%

Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…ZAC is a maternally imprinted gene (12). If the paternal allele were lost, ZAC gene expression would not be influenced; if the maternal allele were lost, ZAC gene expression would be silenced, causing ZAC downregulation (12,13). However, it was not possible to check which allele was lost in the present study.…”

Section: Discussionmentioning

confidence: 79%

“…Differences in the frequency of ZAC gene LOH in the tumor lead to the downregulation of ZAC (13). In previous reports, the frequency of ZAC gene LOH in ovarian (11), breast (3) and squamous cell carcinoma (4) tumors was 36.4, 40 and 31.4%, respectively; in B-cell lymphoma, LOH was identified in 23% (3/11) of cases (8).…”

Section: Discussionmentioning

confidence: 83%

Correlation between gastric carcinoma and ZAC gene-associated microsatellite instability and loss of heterozygosity

Zhu

Yang

et al. 2017

Oncology Letters

View full text Add to dashboard Cite

Abstract. The present study explored the association between loss of heterozygosity (LOH) or microsatellite instability (MSI) of the zinc finger regulator of apoptosis and cell-cycle arrest (ZAC) gene and the clinicopathological factors of gastric cancer. Samples of cancer and cancer-adjacent normal tissue from 30 patients with gastric cancer were collected. The genomic DNA was extracted from each and amplified with primers specific to ZAC microsatellite mutations, then run on a polyacrylamide gel for analysis. The CA197 microsatellite locus exhibited LOH in cancer sample 4. There was LOH in the 15AAAG locus in cancer sample 27 and cancer-adjacent tissue 23, and MSI at 15AAAG in cancer-adjacent tissue 27. There was MSI at the D6S1703 microsatellite locus in cancer-adjacent tissue 28. There was no LOH or MSI in the CA340 microsatellite locus in the gastric cancer or adjacent tissues analyzed. Thus, the frequency of LOH or MSI at ZAC gene-associated microsatellite loci for all patients was 13.3% (4/30). The present study has demonstrated that LOH and MSI events may contribute to the downregulation of ZAC; however, it is unlikely to be the primary cause, as it was only identified in 13.3% of cases.

show abstract

“…Global DNA methylation does not appear to be a marker for infertility as many studies have found no difference between fertile and infertile males [9,11,12], indicating that gene-specific methylation errors are primarily susceptible.…”

Section: Dna Methylation In Sperm Function and Male Infertilitymentioning

confidence: 98%

“…Most studies investigating the association between aberrant DNA methylation and infertility have focused on candidate imprinted genes [8][9][10][11][12]. As imprinted genes in germ cells have unique reprogramming events they are a central target for investigating aberrant methylation errors in sperm from infertile men.…”

Section: Dna Methylation In Sperm Function and Male Infertilitymentioning

confidence: 99%

Sperm DNA Methylation, Infertility and Transgenerational Epigenetics

Carroll¹

2015

GGS

View full text Add to dashboard Cite

show abstract

Methylation status of imprinted genes DLK1-GTL2, MEST (PEG1), ZAC (PLAGL1), and LINE-1 elements in spermatozoa of normozoospermic men, unlike H19 imprinting control regions, is not associated with idiopathic recurrent spontaneous miscarriages

Cited by 18 publications

References 20 publications

Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats

Aberrant methylation of multiple imprinted genes in embryos of tamoxifen-treated male rats

Correlation between gastric carcinoma and ZAC gene-associated microsatellite instability and loss of heterozygosity

Sperm DNA Methylation, Infertility and Transgenerational Epigenetics

Contact Info

Product

Resources

About