Alterations of the FSH and LH receptor genes and evaluation of sperm ultrastructure in men with idiopathic hypergonadotropic hypogonadism.

Purpose: Gonadotropins, interacting with their gonadal receptors, play a key role in sexual development, reproductive functions and metabolism. In this study we performed the genetic analysis of FSHR and LHR and semen investigation in 14 infertile men with normal level of T and elevated levels of FSH and/or LH in the absence of other causes of infertility. Methods: Sperm parameters were analysed following WHO (2010) guidelines and sperm morphology by Transmission Electron Microscopy (TEM) analysis mathematically elaborated. FSHR and LHR gene mutations have been searched by PCR technique, followed by DHPLC analysis and direct sequencing. Results: In FSHR, we found no difference in the frequency between Ala or Thr at position 307, Ser was at codon 680 in all subjects. Three patients had an heterozygous mutation at codon 419. Three intronic polymorphisms (rs2091787, rs6708637, rs1922464) were significantly found compared to controls; the single allele frequency and the odds ratio were calculated. Two new variants: the Cys338Arg and the Gln123Glu were detected in two different patients. Regarding LHR, three patients were heterozygous for the known variant Glu354Lys and two for Ile374Thr. Intronic polymorphisms were not identified. A new variant, the Val144Ile was found. By the routine semen analysis, variable seminal conditions in this group of patients was observed, on the contrary TEM data mathematically elaborated showed a homogeneous decrease in fertility index and increase in sperm pathologies such as apoptosis and immaturity. Conclusions: The obtained results suggest that a deeper examination of spermatozoa, achieved by the use of more powerful tools such as TEM or molecular analysis, are advisable in patients with hypergonadotropic hypogonadism.