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Adenosine Triphosphate-Binding Cassette Superfamily Transporter Gene Expression in Severe Male Infertility¹

^a Medical and Molecular Genetics Center-IRO, Hospital Duran i Reynals, 08907 L'Hospitalet de Llobregat, Barcelona, Spain ^b Andrology Department, Fundació Puigvert, 08025 Barcelona, Spain

ABSTRACT

Cystic fibrosis transmembrane regulator (CFTR), multidrug-resistant (MDR)1, and multidrug resistance-associated (MRP) proteins belong to the ATP-binding cassette (ABC) transporter superfamily. A compensatory regulation of MDR1 and CFTR gene expression has been observed in CFTR knockout rodent intestine and in an epithelial cell line of human colon, whereas a high homology and similar anion binding site are shared by MRP and CFTR proteins. To provide better insight into the relationship among the expression behavior in vivo of the three genes in human testis, analysis of MDR1 and MRP gene expression in testicular biopsies was performed and related to the presence of CFTR gene mutations in congenital absence of the vas deferens (CAVD: n = 20) and non-CAVD (n = 30) infertile patients with azoospermia or severe oligozoospermia. A CFTR mutation analysis performed in both groups of patients supported the involvement of CFTR gene mutations in CAVD phenotype (85%) and in defective spermatogenesis (19%). Quantitative reverse transcription-polymerase chain reaction analysis of testicular tissue showed a CFTR-independent MDR1 and MRP gene expression in human testis, suggesting that the mechanisms underlying CFTR gene regulation in testis are different from those in intestine. These findings should contribute to the understanding of patterns of in vivo expression of CFTR, MDR1, and MRP genes in CFTR-related infertility.

FOOTNOTES

First decision: 11 January 2001.

¹ This work was supported by grants from Fondo de Investigación Sanitaria (FIS) (99/0654), Fundació La Marató TV3 (980410), and Institut Catalá de la Salut. S.L. is supported by Fundació La Marató TV3.

² Correspondence: Teresa Casals, Medical and Molecular Genetics Center- IRO, Hospital Duran i Reynals, 08907 L'Hospitalet de Llobregat, Barcelona, Spain. FAX: 34 93 260 77 76; tcasals{at}iro.es

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