RHOXF2 gene, a new candidate gene for spermatogenesis failure

Area of Science:

• Genetics
• Reproductive Biology
• Molecular Evolution

Background:

• Genes regulating germ cell development evolve rapidly, making them candidates for spermatogenesis impairments.
• RHOXF2, a testis-specific gene on chromosome Xq24, is highly homologous to RHOXF2B.

Purpose of the Study:

• To sequence RHOXF2 and RHOXF2B in patients undergoing intracytoplasmic sperm injection (ICSI).
• To identify single-nucleotide polymorphisms (SNPs) associated with impaired spermatogenesis.

Main Methods:

• Sequencing of RHOXF2 and RHOXF2B exons in 327 ICSI patients (100 with normal, 227 with impaired spermatogenesis).
• Initial sequencing of all four exons in 47 patients, followed by sequencing of exons 2 and 3 in the remaining 280 patients due to high SNP frequency in these regions.

Main Results:

• High sequence identity between RHOXF2 and RHOXF2B precluded distinguishing between them.
• Nine SNPs were identified, but no significant frequency differences were observed between patients with normal and impaired spermatogenesis.
• A 21-nucleotide insertion was found in both groups, while a guanine insertion, causing a premature stop codon, was exclusively identified in two patients with impaired spermatogenesis.

Conclusions:

• RHOXF2 exhibits characteristics of rapid evolution, potentially influenced by positive selection.
• Identified SNPs in RHOXF2 exons 2 and 3 were not correlated with male infertility.
• A specific guanine insertion in RHOXF2 may be linked to impaired spermatogenesis, warranting further investigation into RHOXF2's role in male fertility.