Introduction: Varicocele is found in approximately 20% of adults and adolescents and in 19–41% of men seeking treatment for infertility. Most semen samples of patients with varicocele showed low sperm count, decreased motility, and morphological abnormalities. Infertility in patients with varicocele has a complex and multifactorial etiology, in which genetic alterations and environmental factors contributed to the disease progression, further reducing the spermatozoa quality and leading to infertility. The testicular damage has been attributed to increased scrotal temperatures and venous pressure, accumulation of toxic substances, hypoxia, hormonal dysfunction, autoimmunity, oxidative stress, and apoptosis. Here, I review the available literature regarding the genetic and epigenetic changes associated with varicocele.
Methods: A comprehensive literature search was carried out to assess genetic and epigenetic factors associated with varicocele. Google scholar data base and PubMed has been searched. Epidemiological studies, experimental studies, inquiries or editorials on the mentioned theme published from 2015 until 2022 were included. specific keywords including “varicocele”, “infertility” and “genetic and epigenetic” have been used.
Results: It has been suggested that patients with infertility and varicocele were observed to have significantly increased DNA-damaged sperm. Some studies in patients with varicoceles have reported an association between chromosomal abnormalities and microdeletions in the Y chromosome with the disease. The gametes of infertile men with altered sperm morphology and motility show high rates of chromosomal abnormalities, which originate mostly from meiotic errors. Abnormal meiotic segregation in spermatozoa of men with varicoceles has been reported. Mutations and gene polymorphisms are frequently observed in infertile men with varicocele. Several studies have demonstrated an association between varicocele and polymorphisms, including single-nucleotide polymorphisms (SNPs). Deletions in the mitochondrial DNA (mtDNA) of spermatozoa have been reported in men with varicocele. the expression of several miRNAs associated with oxidative stress in the spermatozoa of patients with varicocele has been evaluated in previous studies and reported reduced expression of miR-15a. miR-15a is also known to repress the expression of HSPA1B. The regulation of the HSPA1B by miR-15a may play an important protective role against cell stress throughout sperm maturation. Thus, these results help elucidate spermatic involvement in the pathology of varicocele.
Conclusion: Because of the multifactorial nature of varicocele, there are still no known biomarkers that could be identified in the early stages of the disease. Chromosomal disorders, mutations, polymorphisms, changes in gene expression, and epigenetic changes have all been reported to be associated with varicocele. Several studies are underway to unravel the genetic basis of this disease, as it is important to understand the origin and the aggravating factors to ensure appropriate guidance and intervention.