背景:由于后代遗传的遗传差异,男性生育力问题变得越来越普遍。非编码RNA(ncRNA)的基因表达和评估,对精子发育至关重要,是重要因素。这种基因的表达会影响精子的活力,因此,生育率。了解在精子分化和发育中起重要作用的复杂蛋白质相互作用至关重要。这些知识可以为男性不育提供更有效的治疗和干预措施。
方法:我们的研究旨在鉴定与非梗阻性无精子症(NOA)有关的新的关键基因和ncRNA,改善遗传诊断,并根据个体的基因型为成功提取精子提供更准确的估计。
结果:我们分析了三名NOA患者的转录本,这些患者的遗传精子问题检测呈阴性,使用微阵列技术对大约50,000个转录序列进行全面的全基因组分析。这比较了NOA精子和正常精子之间的基因表达谱。我们发现显著的基因表达差异:150个基因上调,78个基因下调,与正常情况相比,24个ncRNAs上调,13个ncRNAs下调。通过将我们的结果与单细胞基因组学数据库交叉引用,我们确定了差异表达基因中过度表达的生物过程术语,如“蛋白质定位于内体”和“异源生物运输”。“在上调基因中过度表达的分子功能术语包括电压门控钙通道活性,“\”生长激素释放激素受体活性,“和”唾液酸跨膜转运蛋白活性。“分析显示与NOA精子相关的9个hub基因:RPL34,CYB5B,GOL6A6,LSM1,ARL4A,DHX57、STARD9、HSP90B1和VPS36。
结论:这些基因及其相互作用蛋白可能在生殖细胞异常和不育的病理生理学中起作用。
BACKGROUND: The issue of male fertility is becoming increasingly common due to genetic differences inherited over generations. Gene expression and evaluation of non-coding RNA (ncRNA), crucial for sperm development, are significant factors. This gene expression can affect sperm motility and, consequently, fertility. Understanding the intricate protein interactions that play essential roles in sperm differentiation and development is vital. This knowledge could lead to more effective treatments and interventions for male infertility.
METHODS: Our research aim to identify new and key genes and ncRNA involved in non-obstructive azoospermia (NOA), improving genetic diagnosis and offering more accurate estimates for successful sperm extraction based on an individual\'s genotype.
RESULTS: We analyzed the transcript of three NOA patients who tested negative for genetic sperm issues, employing comprehensive genome-wide analysis of approximately 50,000 transcript sequences using microarray technology. This compared gene expression profiles between NOA sperm and normal sperm. We found significant gene expression differences: 150 genes were up-regulated, and 78 genes were down-regulated, along with 24 ncRNAs up-regulated and 13 ncRNAs down-regulated compared to normal conditions. By cross-referencing our results with a single-cell genomics database, we identified overexpressed biological process terms in differentially expressed genes, such as \"protein localization to endosomes\" and \"xenobiotic transport.\" Overrepresented molecular function terms in up-regulated genes included \"voltage-gated calcium channel activity,\" \"growth hormone-releasing hormone receptor activity,\" and \"sialic acid transmembrane transporter activity.\" Analysis revealed nine hub genes associated with NOA sperm: RPL34, CYB5B, GOL6A6, LSM1, ARL4A, DHX57, STARD9, HSP90B1, and VPS36.
CONCLUSIONS: These genes and their interacting proteins may play a role in the pathophysiology of germ cell abnormalities and infertility.