Transcriptome and genome sequencing investigating the molecular characteristics of patients with varicocele infertility

Abstract

The prevalence of varicoceles in male infertility is increasing; however, the exact mechanism is unknown, and no direct studies of varicose spermatic veins have been conducted. Three patients with varicocele infertility were included to explore the possible factors that cause varicocele infertility, and varicose and nearby normal veins were harvested by varicocelectomy. RNA sequencing was performed on six vascular samples, followed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses of the screened differential expressed genes which were validated by quantitative reverse transcription‐polymerase chain reaction. The genomes of the patients were analysed using next‐generation sequencing to screen for genetic factors behind varicocele infertility. 1171 genes were upregulated and 2772 were downregulated in varicose spermatic veins compared with those in normal veins. These genes were significantly enriched in the alcohol consumption pathway. HIST1H4C, HIST1H4F, HIST1H4K, TM9SF1, and TMEFF1 were significantly differentially expressed. The genomic results identified patients with mutations in CFTR, NANOS1, SRCAP, GATA4, GCM2, TUBB1, ALDH7A1, ANTXR1, and MAP3K1. In conclusion, our results indicated that Alcohol consumption may be a cause of varicoceles. Mutations in certain genes, such as CFTR, may be a cause of male infertility due to varicoceles.

TM9SF1 offers utility as an efficient predictor of clinical severity and mortality among acute respiratory distress syndrome patients

“…Additionally, TM9SF1 protein levels in PBMCs from patients with severe ARDS were also upregulated 2.02-fold compared to those from patients with non-severe ARDS. TM9SF1 has also been linked to a range of other conditions, including certain tumors ( 47 , 48 ), ruptured intracranial aneurysms ( 34 ), and varicose spermatic veins ( 49 ). First identified as a marker associated with autophagy ( 50 ), TM9SF1 has since been confirmed to play roles in autophagic activity and regulating inflammatory factors ( 12 ).…”

The Evolving Landscape of Male Varicocele Pathophysiology in the Era of Multi-Omics: A Narrative Review of the Current Literature

“…Whole-exome sequencing in a cohort of patients with varicoceles has identified multiple genetic variants associated with varicoceles (e.g., AAMP, SPINT1, or MK167) [77]. A recent study of three men with varicoceles performed next-generation RNA sequencing to explore preferentially upregulated genes in men with varicoceles and identified cystic fibrosis transmembrane conductance regulator (CFTR), suggesting a potential role of this protein in the pathogenesis of varicoceles [78]. Although intriguing, this study has not been independently validated and additional studies will be necessary to further characterize the phenotypes of these select gene mutations in a more robust cohort of patients.…”