Research Article Role of Inhibitors of Apoptosis Proteins in Testicular Function and Male Fertility: Effects of Polydeoxyribonucleotide Administration in Experimental Varicocele Letteria Minutoli, 1 Salvatore Arena, 2 Pietro Antonuccio, 2 Carmelo Romeo, 2 Alessandra Bitto, 1 Carlo Magno, 3 Mariagrazia Rinaldi, 1 Antonio Micali, 4 Natasha Irrera, 1 Gabriele Pizzino, 1 Federica Galfo, 1 Francesco Squadrito, 1 Domenica Altavilla, 2 and Herbert Marini 1 1 Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico “G. Martino”, Via Consolare Valeria, 98125 Messina, Italy 2 Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, AOU Policlinico “G. Martino”, Via Consolare Valeria, 98125 Messina, Italy 3 Department of Human Pathology, University of Messina, AOU Policlinico “G. Martino”, Via Consolare Valeria, 98125 Messina, Italy 4 Department of Biomedical Sciences and Morphofunctional Imaging, University of Messina, AOU Policlinico “G. Martino”, Via Consolare Valeria, 98125 Messina, Italy Correspondence should be addressed to Letteria Minutoli; lminutoli@unime.it Received 23 February 2015; Revised 20 April 2015; Accepted 21 April 2015 Academic Editor: Joilson O. Martins Copyright © 2015 Letteria Minutoli et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Neuronal apoptosis inhibitory protein (NAIP) and survivin might play an important role in testicular function. We investigated the efect of PDRN, an agonist of adenosine A2A receptor, on testicular NAIP and survivin expression in an experimental model of varicocele. Afer the creation of experimental varicocele (28 days), adolescent male Sprague-Dawley rats were randomized to one of the following treatments lasting 21 days: vehicle, PDRN (8 mg/kg i.p., daily), PDRN + 3,7-dimethyl-propargylxanthine (DMPX, a specifc adenosine A2A-receptor antagonist, 0.1 mg/kg i.p., daily), varicocelectomy, and varicocelectomy + PDRN (8 mg/kg i.p., daily). Sham-operated animals were used as controls. Animals were then euthanized and testis expression of NAIP and survivin was evaluated through qRT-PCR, western blot, and immunohistochemical analysis. Spermatogenetic activity was also assessed. NAIP and survivin expressions were signifcantly reduced following varicocele induction when compared to sham animals whereas PDRN-treated rats showed an increase in NAIP and survivin levels. Immunohistochemistry revealed an enhanced expression of NAIP and survivin with a characteristic pattern of cellular localization following PDRN treatment. Moreover, administration of PDRN signifcantly restored spermatogenic function in varicocele rats. PDRN may represent a rational therapeutic option for accelerating recovery from depressed testicular function through a strategic modulation of apoptosis in experimental varicocele. 1. Introduction Varicocele is the most common cause of infertility in men [1] and the exact pathophysiological mechanism by which it impairs fertility in afected men remains unknown [2, 3]. Consequently, the early diagnosis of varicocele is necessary before testicular damage might occur and, as indicated by several clinical studies, the varicocele repair is possible through surgical procedure [4–7]. Although many advances have occurred in the treatment of varicocele, it still represents an important and challenging aspect of basic research (male reproductive physiology and endocrinology, pathophysiol- ogy, and pharmacology of reproduction and fertility) and medical practice for urologists, pediatric surgeons, and gen- eral physicians, to date [4–7]. Hindawi Publishing Corporation BioMed Research International Volume 2015, Article ID 248976, 9 pages http://dx.doi.org/10.1155/2015/248976