CFTR gene mutations and male infertility

Abstract

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are a relatively frequent cause of male infertility. Depending on their molecular consequences, CFTR mutations may either result in typical cystic fibrosis (CF), one of the most common autosomal recessive disorders, which is characterized by chronic lung disease, pancreatic exocrine insufficiency, an increase in the concentration of sweat electrolytes and male infertility, due to obstructive azoospermia, or in atypical (often monosymptomatic) forms of CF such as congenital absence of the vas deferens (bi- or unilateral), bilateral ejaculatory duct obstruction or bilateral obstructions within the epididymides. All males with idiopathic obstructive azoospermia bear an increased risk for CF offspring. Couples requesting microsurgical epididymal sperm aspiration and in vitro fertilization, e.g. intracytoplasmic sperm injection, should be offered genetic counselling and molecular genetic analysis of the CFTR gene, if male infertility due to obstructive azoospermia is the underlying cause.

Regulation of Wolffian Duct Development

“…Congenital bilateral absence of the vas deferens is estimated to occur in 1:1,000 to 1:10,000, responsible for 1–2% of cases with male infertility and for 9.6% of cases with obstructive azoospermia [42, 43]. It is thought to result from abnormal development of the WDs, although it is not entirely certain that absence of the vas deferens is always congenital [43].…”

“…It is thought to result from abnormal development of the WDs, although it is not entirely certain that absence of the vas deferens is always congenital [43]. Approximately 80% of cases is caused by mutations on both alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) gene [42]. In patients with relatively mild mutations absence of the vasa deferentia may be the only manifestation of cystic fibrosis [42].…”

“…Approximately 80% of cases is caused by mutations on both alleles of the cystic fibrosis transmembrane conductance regulator (CFTR) gene [42]. In patients with relatively mild mutations absence of the vasa deferentia may be the only manifestation of cystic fibrosis [42]. Congenital bilateral absence of the vas deferens is characterised by absence of the body and tail of the epididymis as well as the vas deferens and seminal vesicles, but the head of the epididymis is consistently present.…”

The Genetics of CFTR: Genotype - Phenotype Relationship, Diagnostic Challenge and Therapeutic Implications

“…Not easier is the task of categorizing the even more heterogeneous oligo-and mono-symptomatic CFTR-RD. In this regard CFTR mutations have been linked to a wide series of pathologies: obstructive azoospermia for CBAVD (Claustres, 2005;Cuppens & Cassiman, 2004;Stuhrmann & Dork, 2000); non-obstructive azoospermia, reduced sperm quality and spermatogenesis defects (Boucher et al, 1999;Dohle et al, 2002;Jakubiczka et al, 1999;Jarvi et al, 1998;Mak et al, 2000;Pallares-Ruiz et al, 1999;van der Ven et al, 1996); male hypofertility due to idiopathic seminal hyperviscosity (Elia et al, 2009;Rossi et al, 2004); female hypofertility due to thick cervical mucus (Gervais et al, 1996;Hayslip et al, 1997); neonatal hypertrypsinaemia with normal sweat test (Castellani et al, 2001a;Gomez Lira et al, 2000;Narzi et al, 2007;Padoan et al, 2002); idiopathic pancreatitis (Castellani et al, 2001b;Gomez Lira et al, 2000;Maire et al, 2003;Pallares-Ruiz et al, 2000); pulmonary diseases (Bombieri et al, 1998;Bombieri et al, 2000); disseminated bronchiectasis (Girodon et al, 1997;Pignatti et al, 1995); chronic rhinosinusitis (Raman et al, 2002;Southern, 2007;Wang et al, 2000b); nasal polyposis (Kerem, 2006;Pawankar, 2003); metabolic alkalosis, hypochloremia, hyponatriemia, hypokalemia and dehydration (Augusto et al, 2008;Kerem, 2006;Leoni et al, 1995;…”

Gastrointestinal Endoscopy and Pathologic Findings

“…For example, in congenital bilateral absence of the vas deferens, patients have mutations in the cystic fibrosis transmembrane conductance regulator gene. This results in defects in the sperm transport system from the mid-epididymis to the seminal vesicles, and most of these men are not candidates for reconstruction [111,112].…”