Cystic fibrosis mutation screening in healthy men with reduced sperm quality

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.

Screening of mutations in the CFTR gene in 1195 couples entering assisted reproduction technique programs

“…21 Unexpectedly, we also found a significant difference in the prevalence of CFTR mutations between males with nonobstructive infertility and the male partners of couples with unexplained infertility. An increased prevalence of CFTR mutations in male subjects with nonobstructive infertility has been reported in previous studies, 22,23 but this association has not been invariably confirmed. 18,24,25 Thus, the relation between CFTR mutations and male infertility requires further assessment.…”

Effect of neonatal exposure to estrogenic compounds on development of the excurrent ducts of the rat testis through puberty to adulthood.

“…The cystic fibrosis transmembrane regulator (CFTR) is a cAMP-activated Cl-channel. It is well established that patients with CF are often infertile due to degeneration of the vas deferens, but some also suffer from obstructive azoospermia due to the deposition of thick mucous material in the epididymal lumen (37,38). There is evidence that a cAMP-activated C1-channel exists in the epididymal epithelium (39,40).…”

“…CFTR may be a good candidate for hormonal regulation because studies on female rats have shown that estrogen up regulates its expression in the uterine epithelium (42,43). In addition, both CF mutations and increased estradiol levels have been found in otherwise healthy men with reduced sperm quality (37,44).…”

Aneuploidy in abortuses following IVF and ICSI

“…A recent review concluded that chromosomal and genetic abnormalities are increased in ICSI offspring as a direct result of underlying parental risk [11]. Furthermore, higher incidences of de novo sex chromosomal aberrations [12][13][14], inheritance of CF mutations and Y microdeletions [15,16] and spermatozoal aneuploidy [17] have been reported following ICSI procedures. ICSI has also been linked to greater embryo fragmentation and lower embryo grade; however, this did not negatively affect implantation or pregnancy rates [18].…”