title: Polydeoxyribonucleotide, an Adenosine-A2AReceptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury.
abstract: Cadmium (Cd) impairs blood-testis barrier (BTB). Polydeoxyribonucleotide (PDRN), an adenosine A2Aagonist, has positive effects on male reproductive system. We investigated the effects of PDRN on the morphological and functional changes induced by Cd in mice testes. Adult Swiss mice were divided into four groups: controls administered with 0.9% NaCl (1 ml/kg, i.p., daily) or with PDRN (8 mg/kg, i.p. daily), animals challenged with Cd chloride (CdCl2; 2 mg/kg, i.p, daily) and animals challenged with CdCl2(2 mg/kg, i.p., daily) and treated with PDRN (8 mg/kg, i.p., daily). Experiments lasted 14 days. Testes were processed for biochemical, structural, and ultrastructural evaluation and hormones were assayed in serum. CdCl2increased pERK 1/2 expression and Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels; it decreased testosterone (TE) and inhibin-B levels and induced structural damages in extratubular compartment and in seminiferous epithelium, with ultrastructural features of BTB disruption. Many TUNEL-positive germ cells were present. CdCl2increased tubular TGF-β3 immunoreactivity and reduced claudin-11, occludin, andN-cadherin immunoreactivity. PDRN administration reduced pERK 1/2 expression, FSH, and LH levels; it increased TE and inhibin-B levels, ameliorated germinal epithelium changes and protected BTB ultrastructure. Few TUNEL-positive germ cells were present and the extratubular compartment was preserved. Furthermore, PDRN decreased TGF-β3 immunoreactivity and enhanced claudin-11, occludin, andN-cadherin immunoreactivity. We demonstrate a protective effect of PDRN on Cd-induced damages of BTB and suggest that PDRN may play an important role against Cd, particularly against its harmful effects on gametogenesis.
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Micali
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Mariagrazia
authors.initials: M
authors.lastname: Rinaldi
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Natasha
authors.initials: N
authors.lastname: Irrera
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Herbert
authors.initials: H
authors.lastname: Marini
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Puzzolo
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy.
authors.forename: Antonina
authors.initials: A
authors.lastname: Pisani
authors.affiliation: Department of Human Pathology, University of Messina Messina, Italy.
authors.forename: Cesare
authors.initials: C
authors.lastname: Lorenzini
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Valenti
authors.affiliation: Department of Veterinary Sciences, University of Messina Messina, Italy.
authors.forename: Rosaria
authors.initials: R
authors.lastname: Laurà
authors.affiliation: Department of Veterinary Sciences, University of Messina Messina, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Germanà
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Pizzino
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pallio
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy.
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.affiliation: Department of Clinical and Experimental Medicine, University of Messina Messina, Italy.
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
keywords: PDRN; TGF-β3; TUNEL; blood-testis barrier; cadmium; immunohistochemistry; pERK 1/2; transmission electron microscopy