Adenosine triphosphate-binding cassette superfamily transporter gene expression in severe male infertility

Cystic fibrosis transmembrane regulator (CFTR), multidrug-resistant (MDR)1, and multidrug resistance-associated (MRP) proteins belong to the ATP-bindi ng cassette (ABC) transporter superfamily. A compensatory regulation of MDR 1 and CFTR gene expression has been observed in CFTR knockout rodent intest ine 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 prov ide better insight into the relationship among the expression behavior in v ivo of the three genes in human testis, analysis of MDR1 and MRP gene expre ssion in testicular biopsies was performed and related to the presence of C FTR gene mutations in congenital absence of the vas deferens (CAVD: n = 20) and non-CAVD (n = 30) infertile patients with azoospermia or severe oligoz oospermia. A CFTR mutation analysis performed in both groups of patients su pported the involvement of CFTR gene mutations in CAVD phenotype (85%) and in defective spermatogenesis (19%). Quantitative reverse transcription-poly merase chain reaction analysis of testicular tissue showed a CFTR-independe nt MDR1 and MRP gene expression in human testis, suggesting that the mechan isms underlying CFTR gene regulation in testis are different from those in intestine. These findings should contribute to the understanding of pattern s of in vivo expression of CFTR, MDR1, and MRP genes in CFTR-related infert ility.