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Beyond obstructive azoospermia: emerging insights into reproductive health in men with cystic fibrosis.

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Τίτλος: Beyond obstructive azoospermia: emerging insights into reproductive health in men with cystic fibrosis.
Συγγραφείς: Crafa A; University of Catania, Catania, Italy., Calogero AE; University of Catania, Catania, Italy., Vij SC; University of Texas at Austin Dell Medical School, Austin, United States., Cannarella R; University of Catania, Catania, Italy. rossella.cannarella@unict.it.
Πηγή: Journal of assisted reproduction and genetics [J Assist Reprod Genet] 2026 Aug; Vol. 43 (8), pp. 2307-2314. Date of Electronic Publication: 2026 May 18.
Τύπος έκδοσης: Journal Article; Review
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Springer Country of Publication: Netherlands NLM ID: 9206495 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-7330 (Electronic) Linking ISSN: 10580468 NLM ISO Abbreviation: J Assist Reprod Genet Subsets: MEDLINE
Imprint Name(s): Publication: <2004- >: Amsterdam : Springer
Original Publication: New York : Plenum Press, c1992-
Ιατρικοί όροι (MeSH): Azoospermia*/genetics , Azoospermia*/pathology , Cystic Fibrosis Transmembrane Conductance Regulator*/genetics , Cystic Fibrosis*/genetics , Cystic Fibrosis*/complications , Cystic Fibrosis*/pathology , Infertility, Male*/genetics , Infertility, Male*/pathology, Spermatogenesis/genetics ; Vas Deferens/pathology ; Vas Deferens/abnormalities ; Spermatozoa/pathology ; Spermatozoa/metabolism ; Sertoli Cells/pathology ; Sertoli Cells/metabolism ; Humans ; Male ; Mutation ; Reproductive Health ; Male Urogenital Diseases
Περίληψη: Cystic fibrosis (CF) is a genetic disorder caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and is classically associated with male infertility due to obstructive azoospermia secondary to congenital bilateral absence of the vas deferens. Increasing evidence suggests that CFTR dysfunction may also contribute to nonobstructive forms of male infertility. Accordingly, CFTR is widely expressed throughout the male reproductive tract, including Sertoli cells, germ cells, and mature spermatozoa. This review summarizes current evidence linking CFTR mutations and variants to hypogonadism, impaired spermatogenesis, altered sperm function, and reduced reproductive outcomes. Clinical studies indicate a high prevalence of testosterone deficiency in men with CF or CBAVD, often occurring in the presence of normal gonadotropin levels. Genetic and meta-analytic data support an association between CFTR variants, particularly the IVS8-5 T polymorphism, and nonobstructive azoospermia. Experimental studies further demonstrate that CFTR plays a critical role in spermatogenesis via regulation of the cAMP-CREB signaling pathway in Sertoli cells and through modulation of microRNA expression affecting germ cell proliferation. CFTR expression in spermatozoa is also implicated in capacitation, motility, and fertilizing capacity through coordinated chloride and bicarbonate transport and interactions with SLC26 family members. Emerging evidence additionally suggests a role for CFTR in early embryonic development, with potential implications for assisted reproductive technology outcomes. Collectively, these findings challenge the traditional view of CF-related male infertility as purely obstructive and highlight CFTR mutations as a potential contributor to nonobstructive infertility. Further studies are required to clarify pathogenic mechanisms and explore targeted therapeutic strategies.
(© 2026. The Author(s).)
Competing Interests: Declarations. Ethics approval: Not applicable. Consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.
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Contributed Indexing: Keywords: CFTR; Cystic fibrosis; Hypogonadism; Male infertility; Nonobstructive azoospermia
Substance Nomenclature: 126880-72-6 (Cystic Fibrosis Transmembrane Conductance Regulator)
0 (CFTR protein, human)
SCR Disease Name: Congenital bilateral aplasia of vas deferens
Entry Date(s): Date Created: 20260517 Date Completed: 20260922 Latest Revision: 20260925
Update Code: 20260925
PubMed Central ID: PMC13597972
DOI: 10.1007/s10815-026-03896-0
PMID: 42144530
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1573-7330
DOI:10.1007/s10815-026-03896-0