Immunohystochemical analysis of CFTR in normal and disrupted spermatogenesis

Cystic fibrosis is the most frequent autosomal recessive disease in the Caucasian population, with an incidence of 1:2500 newborn and a frequency of 1:25. The associated gene is Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and it encodes the CFTR protein that functions as a chloride (Cl(-)) channel. It is found in the apical membrane of exocrine epithelial cells, responsible for the regulation of the movement of water and solutes through biological membranes. To our knowledge, there are no studies on protein localization in the different cell types of the seminiferous epithelium with different pathologies. The aim of the present study was to analyze the expression of the CFTR protein in the human seminiferous epithelium of infertile males with different pathologies. CFTR protein expression was studied by immunohistochemistry in paraffin sections of testicular biopsies of six infertile men: Sertoli cell only syndrome, maturation arrest, secondary obstructive azoospermia, primary obstructive azoospermia due to congenital bilateral absence of the vas deferens (CBAVD), severe oligozoospermia, and retrograde ejaculation. All cell types of the seminiferous epithelium were studied: Sertoli cells, spermatogonia, primary spermatocytes at the leptotene/zygotene and at the pachytene stages, secondary spermatocytes, round, elongating and elongated spermatids, and spermatozoa. With the exception of sperm, all cells were labeled in the cytoplasm and in the cytoplasmic membrane. In the patient with CBAVD labeling was light at the cell membrane and absent in the cytoplasm of Sertoli cells and diploid germ cells. Generally, labeling was stronger after the diploid stage, which is probably related to cell volume reduction during spermiogenesis. The results obtained also suggest that the CFTR protein may impact CBAVD spermatogenesis and other pathologies.