title: DAX-1 and DAX-1A expression in human testicular tissues with primary spermatogenic failure.
abstract: DAX-1 [dosage-sensitive sex reversal-adrenal hypoplasia congenital (AHC) critical region on the X chromosome gene 1; NR0B1] is an orphan nuclear receptor that acts as a transcriptional repressor in adrenal/gonadal development, steroidogenesis and probably spermatogenesis. An alternatively spliced form called DAX-1A (NR0B1A) has been described in several tissues including the testis, and in vitro studies have shown an inhibitory effect on DAX-1 transcriptional function. We aimed to study the mRNA and protein expression of DAX-1 in testicular tissues of 65 men with primary spermatogenic failure [complete Sertoli cell only syndrome (SCOS), focal SCOS, maturation arrest and mixed atrophy] compared with 33 controls with normal spermatogenesis. As a novel finding, we observed intense immunostaining, not only in the nucleus of Sertoli cells, but also in pachytene spermatocytes and round spermatids. The quantitative mRNA expression of DAX-1 and DAX-1A was similar between cases and controls and was not associated with the levels of gonadotrophins and steroids. Moreover, DAX-I transcript expression level was ∼750-fold higher than DAX-1A, and there was a strong positive correlation between them (r = 0.52; P< 0.001). We conclude that, in addition to Sertoli cells, DAX-1/DAX-1A is expressed in germ cells from spermatogonia to round spermatids. Besides, the similar mRNA expression of DAX-I and DAX-IA in testicular tissues from cases and controls does not support the involvement of DAX-1 in the etiology of primary spermatogenic failure. Finally, the low level of expression of the alternative transcriptional variant DAX-1A would not support its putative inhibitory function in vivo.
authors.affiliation: Institute of Maternal and Child Research, School of Medicine,  University of Chile, Santiago P.C. 8360160,  Chile.
authors.forename: M C
authors.initials: MC
authors.lastname: Lardone
authors.forename: A
authors.initials: A
authors.lastname: Parada-Bustamante
authors.forename: M
authors.initials: M
authors.lastname: Ebensperger
authors.forename: R
authors.initials: R
authors.lastname: Valdevenito
authors.forename: E
authors.initials: E
authors.lastname: Kakarieka
authors.forename: D
authors.initials: D
authors.lastname: Martínez
authors.forename: R
authors.initials: R
authors.lastname: Pommer
authors.forename: A
authors.initials: A
authors.lastname: Piottante
authors.forename: A
authors.initials: A
authors.lastname: Castro
mesh_terms: D000328:Adult; D017398:Alternative Splicing; D016022:Case-Control Studies; D002677:Chile; D057137:DAX-1 Orphan Nuclear Receptor / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006062:Gonadotropins / Q000096:biosynthesis; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D060888:Real-Time Polymerase Chain Reaction; D012098:Reproduction / Q000235:genetics*; D054331:Sertoli Cell-Only Syndrome / Q000235:genetics*; D012708:Sertoli Cells / Q000378:metabolism* / Q000473:pathology; D013087:Spermatids / Q000166:cytology / Q000378:metabolism; D013090:Spermatocytes / Q000166:cytology / Q000378:metabolism; D013091:Spermatogenesis; D013093:Spermatogonia / Q000166:cytology / Q000378:metabolism; D013256:Steroids / Q000096:biosynthesis
chemical_list: D057137:DAX-1 Orphan Nuclear Receptor; D006062:Gonadotropins; C539965:NR0B1 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D013256:Steroids