Mutation screening of the FSH receptor gene in infertile men.

Follicle stimulating hormone (FSH) is important for controlling spermatogenesis through binding with its receptor. However, little information is available on mutations of the FSH and its receptor gene in infertile men. To study the genetic defects, which caused problems in spermatogenesis, we screened the point mutations of the FSH receptor gene in infertile men with high serum FSH concentrations. Seventy male infertile patients with high FHS levels (> 12 mIU/ml) were screened for mutations in each of the 10 exons of the FSH receptor gene, using genomic DNA PCR and a single-strand conformation polymorphism (SSCP) analysis. From this study, three shifted bands were detected by SSCP. The first shifted band was found in the PCR product of exon 4, including the exon-intron boundary sequence in only one patient. The sequence analysis revealed a nucleotide A to T substitution in intron 3 (IVS3-4A-->T). The second shifted band was detected in exon 10 with high frequency (33%). A nucleotide A to G substitution was found at the position of the 994th nucleotide, predicting a Thr to Ala substitution at the position of the 307th amino acid (Thr307Ala). The third shifted band in the 3' region of exon 10 was detected frequently in infertile patient and normal groups. It was tightly linked to the Thr307Ala variant. Thus, all of the abnormalities represent neutral polymorphisms, and not pathological mutations of the FSH receptor gene. In conclusion, we did not confirm that the genomic mutation of the FSH receptor is a major genetic cause in Korean infertile patients with high FSH levels.