Endocrine Abstracts

Introduction: Inactivating mutations in LH or FSH receptors (R) are known causes of gonadotrophins resistance.

Aim: This study aims at evaluating the presence of mutations and polymorphisms of FSHR and LHR and sperm quality in men with hypergonadotropic hypogonadism without obvious testicular noxa.

Patients and methods: We selected 8 males with elevated levels of FSH and/or LH and normal levels of testosterone. Sperm parameters were analysed following WHO (1999) guidelines and by transmission electron microscopy (TEM). Elaborated TEM data provided the percentage of sperm pathologies and the number of structurally normal sperm (fertility index). The PCR technique, followed by DHPLC analysis and direct sequencing, enabled to investigate FSHR and LHR gene mutations.

Results: For LHR, 2/8 patients were heterozygous for Ile374Thr mutation and 1/8 for Glu354Lys substitution. Regarding FSHR, 4/8 were heterozygous for Ala419Thr mutation and 2/8 were homozygous for Ala307Thr mutation. We also found in one patient a new mutation (Cys338Arg) localized in the extracellular domain of FSHR. Minor allele frequencies of 43.75% for polymorphism rs6708637 and of 37.5% for polymorphism rs1922464 were observed, both similar to those reported in the general population. A minor allele frequency of 37.5% of polymorphism rs2091787, higher than that reported for the general population (24%), was observed. Two patients were azoospermic, 4/6 patients showed reduced sperm concentration, 6/6 reduced sperm motility, 4/6 high percentage of apoptosis and immaturity, 5/6 increased percentage of necrosis. The fertility index was reduced in all patients.

Conclusions: The relationship between the different mutations (included the new found mutation Cys338Arg in FSHR) and altered semen parameters deserves attention and further studies.

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 research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.