Endocrine Abstracts

Introduction: Recently, a single nucleotide polymorphism (SNP) in the FSH (FSH)-β gene (FSHB −211G>T, rs10835638) that leads to reduced mRNA transcription was associated with serum FSH levels in an Estonian cohort of young men (Grigorova et al., Hum Reprod 2008). Further investigations showed an increased frequency of the T-allele in patients with oligozoospermia compared to men with normozoospermia (Grigorova et al., JCEM 2010). Another Baltic study (Grigorova et al., JCEM 2011) revealed significant associations with additional reproductive parameters (e.g. testicular volume). Since the three previous studies are limited to men from the Baltic area, a comparable approach was undertaken with patients from the Centre of Reproductive Medicine in Münster.

Methods: A large number of 1213 patients visiting for infertility workup (615 with normal and 598 with reduced sperm concentration, cut-off 20 Mill./ml) were retrospectively selected. Patients with known causes for male infertility (e.g. cryptorchidism, infections, chromosomal aberrations) were excluded. The SNP in the FSHB gene was analysed by TaqMan assay.

Results: The T-allele frequency was higher in the oligozoospermic group compared with men with normal sperm concentration (18.1 vs 14.7%, P=0.023). The T-allele showed significant dosage effects (each P<0.05) for FSH (−0.56 U/l per T-allele), LH (0.27 U/l) and bi-testicular volume (−5.0 ml). Fitting trends were found for associations with sperm concentration (−7.5 Mill./ml, P=0.057) and total sperm count (−24.1 Mill./ml, P=0.088). Meta-analysis of all published studies – comprising 3017 men in total – confirmed highly significant associations for FSH, LH and testicular volume. In addition, a significantly different distribution of genotypes between normo- and oligozoospermic men was found in the pooled analysis for the first time (P=0.0052).

Conclusions: The associations between FSHB genotype and serum FSH as well as testicular volume were confirmed in our study population and in the meta-analysis and further substantiate the FSHB −211G>T SNP as a novel risk factor for male infertility. Whether T-allele carriers benefit from FSH treatment remains to be elucidated.

Supported by a grant from the Alexander-von-Humboldt foundation.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.