• PMID: 25780578
• Gene Name: RHOXF2
• Condition: Spermatogenic failure
• Association: Associated
• Population size: 227
• Population details: 227 displayed impaired spermatogenesis
• Sex: Male
• Infertility type: Male infertility

RHOXF2 gene, a new candidate gene for spermatogenesis failure

Frainais C, Kannengiesser C, Albert M, Molina-Gomes D, Boitrelle F, Bailly M, Grandchamp B, Selva J, Vialard F.

INTRODUCTION: Genes involved in testicular differentiation, spermatogenesis, proliferation and apoptosis of germ cells have been shown to evolve rapidly and display rapid DNA changes. These genes are therefore good candidates for explaining impairments in spermatogenesis. Initial studies of some of these genes appear to confirm this hypothesis. The RHOXF2 candidate gene belongs to the RHOX family clustered in Xq24 and is specifically expressed in the testis. It contains four exons and codes for a 288 amino acid (aa) transcription factor. It has a high degree of homology (>99.9%) with its paralogue RHOXF2B, which is also preferentially expressed in the testis. OBJECTIVES: To sequence RHOXF2 and RHOXF2B in intracytoplasmic sperm injection (ICSI) patients and identify any single-nucleotide polymorphisms (SNPs) associated with impaired spermatogenesis. MATERIALS: A cohort of 327 patients in ICSI programmes at Poissy and Bichat hospitals. All patients gave their written, informed consent to participation. One hundred patients had unaffected spermatogenesis and 227 displayed impaired spermatogenesis. METHODS: The four exons in each of RHOXF2 and RHOXF2B were sequenced in 47 patients with oligospermia or non-obstructive azoospermia. Given that exons 2 and 3 were found to harbour most of the SNPs, only these two exons were sequenced in the remaining 280 subjects. RESULTS: Due to the extremely high degree of sequence identity between RHOXF2 and RHOXF2B, we were not able to distinguish between the sequences of these two genes. Although 9 SNPs were identified, there were no significant frequency differences between ICSI patients with normal vs. impaired spermatogenesis. Two insertions were identified: a 21-nucleotide insertion was retrieved in both groups and a guanine insertion (inducing a premature stop codon) only found in two patients with impaired spermatogenesis. CONCLUSION/OUTLOOK: RHOXF2 is a good candidate for rapid evolution by positive selection. Analysis of the polymorphism frequency in exons 2 and 3 did not allow us to correlate the identified SNPs with male infertility. However, a single nucleotide insertion was identified only in men with impaired spermatogenesis. Further work will be needed to establish whether genetic changes in RHOXF2 can give rise to defects in spermatogenesis. FAU - Frainais, Christophe AU - Frainais C AD - Laboratoire Clement, Le Blanc Mesnil, F-93110 France. FAU - Kannengiesser, Caroline AU - Kannengiesser C AD - Department of Genetics, Hôpital Bichat, Paris, F-75018 France. FAU - Albert, Martine AU - Albert M AD - EA 2493, University of Versailles Saint-Quentin, Versailles, F-78035 France ; Department of Reproductive Biology, Cytogenetics, Gynecology and Obstetrics, Poissy Saint Germain Hospital, Poissy, F-78303 France. FAU - Molina-Gomes, Denise AU - Molina-Gomes D AD - Department of Reproductive Biology, Cytogenetics, Gynecology and Obstetrics, Poissy Saint Germain Hospital, Poissy, F-78303 France. FAU - Boitrelle, Florence AU - Boitrelle F AD - EA 2493, University of Versailles Saint-Quentin, Versailles, F-78035 France ; Department of Reproductive Biology, Cytogenetics, Gynecology and Obstetrics, Poissy Saint Germain Hospital, Poissy, F-78303 France. FAU - Bailly, Marc AU - Bailly M AD - Department of Reproductive Biology, Cytogenetics, Gynecology and Obstetrics, Poissy Saint Germain Hospital, Poissy, F-78303 France. FAU - Grandchamp, Bernard AU - Grandchamp B AD - Department of Genetics, Hôpital Bichat, Paris, F-75018 France. FAU - Selva, Jacqueline AU - Selva J AD - EA 2493, University of Versailles Saint-Quentin, Versailles, F-78035 France ; Department of Reproductive Biology, Cytogenetics, Gynecology and Obstetrics, Poissy Saint Germain Hospital, Poissy, F-78303 France.