title: Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival.
abstract: Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.
authors.affiliation: Departments of *Biology, Ecology and Earth Sciences (Di.B.E.S.T.) †Department of Pharmacy and Health and Nutritional Sciences, University of Calabria, Arcavacata di Rende ‡Post-graduate School in Clinical Pathology §Centro Sanitario, University of Calabria, Rende, Cosenza, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Perrotta
authors.forename: Mariarita
authors.initials: M
authors.lastname: Perri
authors.forename: Marta
authors.initials: M
authors.lastname: Santoro
authors.forename: Salvatore
authors.initials: S
authors.lastname: Panza
authors.forename: Maria C
authors.initials: MC
authors.lastname: Caroleo
authors.forename: Carmela
authors.initials: C
authors.lastname: Guido
authors.forename: Annamaria
authors.initials: A
authors.lastname: Mete
authors.forename: Erika
authors.initials: E
authors.lastname: Cione
authors.forename: Saveria
authors.initials: S
authors.lastname: Aquila
mesh_terms: D001692:Biological Transport; D015153:Blotting, Western; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D004801:Eosine Yellowish-(YS); D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D018168:Receptors, Retinoic Acid / Q000235:genetics* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D013085:Spermatic Cord / Q000378:metabolism / Q000473:pathology; D013094:Spermatozoa / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D014646:Varicocele / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: C000607071:RARA protein, human; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014212:Tretinoin; D002784:Cholesterol; D004801:Eosine Yellowish-(YS)