BackgroundMale infertility is a complex disease caused by a combination of genetic, environmental, and lifestyle factors. Abnormal epigenetic programming has been proposed as a possible mechanism compromising male fertility. Recent studies suggest that aberrant imprinting in spermatozoa in a subset of infertile men is a risk factor for congenital diseases in children conceived via assisted reproduction techniques. In this study, we examined the DNA methylation status of CpG sites within the differentially methylated regions (DMRs) of three imprinted genes, H19, GNAS, and DIRAS3, using combined bisulfite PCR restriction analysis and bisulfite sequencing in sperm obtained from 135 men with idiopathic male infertility, including normozoospermia (n = 39), moderate oligozoospermia (n = 45), and severe oligozoospermia (n = 51), and fertile controls (n = 59). The percentage of global methylation was compared between fertile controls and infertile patients displaying abnormal DNA methylation status of imprinted loci. Moreover, we also analyzed whether the DNA methyltransferases (DNMTs) polymorphisms impact upon the methylation patterns of imprinted genes in idiopathic infertile males.ResultsAberrant methylation patterns of imprinted genes were more prevalent in idiopathic infertile males, especially in patients with oligozoospermia. Infertile males with aberrant methylation patterns of imprinted genes displayed a tendency of lower global methylation levels, although not reaching statistical significance (P = 0.13). In the genotype-epigenotype correlation analysis, no significant association was observed between aberrant methylation patterns of the three imprinted genes and genotypes of the four DNA methyltransferase (DNMT) genes.ConclusionWe conclude that abnormalities of DMR within imprinted genes may be associated with idiopathic male infertility. Disruption in methylation pattern of the three imprinted genes does not occur in high-risk genotypes of DNMTs.Electronic supplementary materialThe online version of this article (10.1186/s13148-018-0568-y) contains supplementary material, which is available to authorized users.

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Oral squamous cell carcinoma (OSCC) still threatens people's daily life. METTL14 is a newly discovered methyltransferase that catalyzes m6A methylation. Hence, this research was carried out to investigate the action mechanism of METTL14 in OSCC. The SCC-4 and UM2 cells, and tumorigenicity assay were utilized to investigate METTL14 roles <i>in vitro</i> and<i> in vivo</i>. Bioinformatic analysis was carried out with the UCSC, TCGA database and The Human Protein Atlas. The gene expression at mRNA and protein levels were measured by qRT-PCR and Western blot. In addition, cell growth and metastasis was analyzed by colony formation and transwell assays. MeRIP assay was performed to test the m6A levels of CALD1. The METTL14 and CALD1 levels were prominently expressed in OSCC cells. METTL14 silencing depleted the cell growth and metastasis. Furthermore, METTL14 silencing depleted the tumor growth <i>in vivo</i>. Additionally, the mRNA and m6A levels of CALD1 were depleted after METTL14 silencing. Overexpressed CALD1 neutralized the si-METTL14 effects in OSCC cells. In conclusion, METTL14 participated in the OSCC progression through modulating the mRNA and m6A levels of CALD1.

Macrosomia is a common perinatal complication, with a series of adverse effects on newborns and pregnant women. However, the effects of long non-coding RNAs (lncRNAs) on non-diabetic fetal macrosomia (NDFMS) remain unclear. The aim of the present study was to investigate whether aberrant lncRNA expression in the placenta is involved in the pathogenesis of NDFMS and to elucidate its biological mechanisms. The expression profile of lncRNAs in the placentas of pregnant women with NDFMS was investigated using an Agilent Human LncRNA Microarray. Differentially expressed lncRNAs were selected for validation using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Additionally, the function of lncRNA ubiquitin-specific peptidase 2 antisense RNA 1 ( USP2-AS1 ) was investigated using a trophoblast cell line. The results revealed that 763 lncRNAs were upregulated and 129 lncRNAs were downregulated in the placentas of women in the NDFMS group (|FC| ≥2.0). A total of 10 lncRNAs (|FC| ≥4.0, signal value ≥50) were selected for validation using two-stage RT-qPCR, indicating that the expression trends of the 10 differentially expressed lncRNAs in the NDFMS group (n=8 vs. 8 and 48 vs. 48) were consistent with the microarray data. In addition, a significant downregulation in the levels of lncRNA USP2-AS1 was observed in both the microarray data and second-stage verification. The overexpression of lncRNA USP2-AS1 induced G1 phase cell cycle arrest and the number of cells entering S phase was reduced. In addition, the viability of HTR-8/SVneo cells was significantly inhibited when lncRNA USP2-AS1 was overexpressed. Therefore, these findings demonstrated that lncRNAs were significantly differentially expressed in the placentas of pregnant women with NDFMS and that the downregulation of lncRNA USP2-AS1 may be involved in the pathogenesis of NDFMS, by promoting trophoblast cell viability.

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