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Polydeoxyribonucleotide, an Adenosine-A2 A Receptor Agonist, Preserves Blood Testis Barrier from Cadmium-Induced Injury

Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Squadrito, Francesco;
Affiliation
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy
Micali, Antonio;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Rinaldi, Mariagrazia;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Irrera, Natasha;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Marini, Herbert;
Affiliation
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy
Puzzolo, Domenico;
Affiliation
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy
Pisani, Antonina;
Affiliation
Department of Human Pathology, University of Messina Messina, Italy
Lorenzini, Cesare;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Valenti, Andrea;
Affiliation
Department of Veterinary Sciences, University of Messina Messina, Italy
Laurà, Rosaria;
Affiliation
Department of Veterinary Sciences, University of Messina Messina, Italy
Germanà, Antonino;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Bitto, Alessandra;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Pizzino, Gabriele;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Pallio, Giovanni;
Affiliation
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina Messina, Italy
Altavilla, Domenica;
Affiliation
Department of Clinical and Experimental Medicine, University of Messina Messina, Italy
Minutoli, Letteria

Cadmium (Cd) impairs blood-testis barrier (BTB). Polydeoxyribonucleotide (PDRN), an adenosine A 2A agonist, 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 (CdCl 2 ; 2 mg/kg, i.p, daily) and animals challenged with CdCl 2 (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. CdCl 2 increased 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. CdCl 2 increased tubular TGF-β3 immunoreactivity and reduced claudin-11, occludin, and N -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, and N -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.

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License Holder: Copyright © 2017 Squadrito, Micali, Rinaldi, Irrera, Marini, Puzzolo, Pisani, Lorenzini, Valenti, Laurà, Germanà, Bitto, Pizzino, Pallio, Altavilla and Minutoli.

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