Abstract:
Background: Infertility remains a global health problem with male-factor infertility accounting for around 50% of cases. Understanding the molecular markers for the male contribution of live birth success has been limited. Here, we evaluated the expression levels of seminal plasma extracellular vesicle (spEV) non-coding RNAs (ncRNAs) in men of couples in relation with those with and without a successful live birth after infertility treatment. Method: Sperm-free spEV small RNA profiles were generated from 91 semen samples collected from male participants of couples undergoing assisted reproductive technology (ART) treatment. Couples were classified into two groups based on successful live birth (yes, n = 28) and (no, n = 63). Mapping of reads to human transcriptomes followed the order: miRNA > tRNA > piRNA > rRNA> \"other\" RNA > circRNA > lncRNA. Differential expression analysis of biotype-specific normalized read counts between groups were assessed using EdgeR (FDR<0.05). Result: We found a total of 12 differentially expressed spEV ncRNAs which included 10 circRNAs and two piRNAs between the live birth groups. Most (n = 8) of the identified circRNAs were downregulated in the no live birth group and targeted genes related to ontology terms such as negative reproductive system and head development, tissue morphogenesis, embryo development ending in birth or egg hatching, and vesicle-mediated transport. The differentially upregulated piRNAs overlapped with genomic regions including coding PID1 genes previously known to play a role in mitochondrion morphogenesis, signal transduction and cellular proliferation. Conclusion: This study identified novel ncRNAs profiles of spEVs differentiating men of couples with and without live birth and emphasizes the role of the male partner for ART success.
摘要:
背景:不孕症仍然是一个全球性的健康问题,男性因素不育症约占病例的50%。了解男性对活产成功的贡献的分子标记是有限的。这里,我们评估了不育治疗后有或没有成功活产的夫妇男性精浆细胞外囊泡(spEV)非编码RNA(ncRNA)的表达水平。方法:从接受辅助生殖技术(ART)治疗的男性参与者收集的91份精液样本中产生无精子spEV小RNA谱。根据成功的活产将夫妇分为两组(是的,n=28)和(不,n=63)。将读段映射到人转录组的顺序为:miRNA>tRNA>piRNA>rRNA>\"其他\"RNA>circRNA>lncRNA。使用EdgeR(FDR<0.05)评估组间生物型特异性标准化读段计数的差异表达分析。结果:我们发现在活产组之间总共有12个差异表达的spEVncRNAs,其中包括10个circRNAs和2个piRNAs。大多数(n=8)已鉴定的circRNAs在无活产组中被下调,并且与本体论相关的目标基因,例如阴性生殖系统和头部发育,组织形态发生,胚胎发育以出生或卵孵化结束,和囊泡介导的转运。差异上调的piRNAs与基因组区域重叠,包括以前已知在线粒体形态发生中起作用的编码PID1基因。信号转导和细胞增殖。结论:这项研究鉴定了spEV的新ncRNAs谱,可区分有活产和无活产的夫妇的男性,并强调了男性伴侣在ART成功中的作用。