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Cystic fibrosis mutation screening in healthy men with reduced sperm quality
K van der Ven1, L Messer, H van der Ven
1Department of Obstetrics and Gynecology, University of Bonn, Germany.
Insights
Cystic fibrosis (CF) gene mutations are more common in infertile men without congenital bilateral absence of the vas deferens (CBAVD). This suggests the CFTR protein impacts sperm development beyond its role in male reproductive tract formation.
Area of Science:
- Genetics
- Reproductive Medicine
- Molecular Biology
Background:
- Cystic Fibrosis (CF) typically causes male infertility via congenital bilateral absence of the vas deferens (CBAVD).
- CF can present as isolated CBAVD or with broader symptoms affecting fertility.
- Emerging evidence suggests CFTR gene involvement in male infertility beyond CBAVD.
Purpose of the Study:
- To investigate the role of the CFTR gene in male infertility unrelated to CBAVD.
- To determine if CFTR mutations contribute to reduced sperm quality or azoospermia in men without CBAVD.
Main Methods:
- Screened semen samples from 127 infertile men for 13 common CFTR gene mutations.
- Included men with reduced sperm quality and azoospermia, excluding those with CBAVD.
- Compared mutation frequencies to a control group of 26 men with normal semen parameters and local CF carrier frequencies.
Main Results:
- 17.5% of men with reduced sperm quality and 14.3% with azoospermia carried at least one CFTR mutation.
- The mutation frequency in infertile men was significantly higher than expected for the general population (P = 0.00139).
- No CFTR mutations were detected in the control group with normal semen parameters.
Conclusions:
- CFTR gene mutations are significantly more prevalent in infertile men with reduced sperm quality or azoospermia, even without CBAVD.
- These findings indicate the CFTR protein plays a role in spermatogenesis and/or sperm maturation.
- The CFTR gene's influence on male fertility extends beyond its established role in the development of the vas deferens.
Abstract:
The majority of men with cystic fibrosis (CF) are infertile due to a bilateral congenital absence of the vas deferens (CBAVD). However, clinically affected CF patients present a spectrum of genital phenotypes ranging from normal fertility to severely impaired spermatogenesis and CBAVD. Recently, it has become apparent that CF can manifest itself as isolated CBAVD in the absence of other clinical symptoms. The present study was undertaken to test the possible involvement of the CF gene in the aetiology of male infertility other than CBAVD. Semen specimens from 127 unrelated healthy males with various diagnoses of reduced sperm quality were screened for a panel of 13 mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Fourteen of 80 (17.5%) healthy men with infertility due to reduced sperm quality and 3 of 21 (14.3%) men with azoospermia had at least one CF mutation (one azoospermic male was a compound heterozygote). The frequency of mutations in our sample of infertile males was significantly higher than the expected CF carrier frequency in the local population (P = 0.00139). No mutations were found in a control group of 26 individuals with normal semen parameters. This increased frequency of CF mutations in healthy men with reduced sperm quality and in men with azoospermia without CBAVD suggests that the CFTR protein may be involved in the process of spermatogenesis or sperm maturation apart from playing a critical role in the development of the epididymal glands and the vas deferens.