Role of Inhibitors of Apoptosis Proteins in Testicular Function and Male Fertility: Effects of Polydeoxyribonucleotide Administration in Experimental Varicocele.
Neuronal apoptosis inhibitory protein (NAIP) and survivin might play an important role in testicular function. We investigated the effect of PDRN, an agonist of adenosine A2A receptor, on testicular NAIP and survivin expression in an experimental model of varicocele. After 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 specific 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 significantly 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 significantly 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.
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Letteria
L
Minutoli
Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Salvatore
S
Arena
Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Pietro
P
Antonuccio
Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Carmelo
C
Romeo
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Alessandra
A
Bitto
Department of Human Pathology, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Carlo
C
Magno
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Mariagrazia
M
Rinaldi
Department of Biomedical Sciences and Morphofunctional Imaging, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Antonio
A
Micali
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Natasha
N
Irrera
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Gabriele
G
Pizzino
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Federica
F
Galfo
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Francesco
F
Squadrito
Department of Paediatric, Gynaecological, Microbiological and Biomedical Sciences, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Domenica
D
Altavilla
Department of Clinical and Experimental Medicine, University of Messina, AOU Policlinico "G. Martino", Via Consolare Valeria, 98125 Messina, Italy.
Herbert
H
Marini
D058917:Adenosine A2 Receptor Antagonists / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D005298:Fertility / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis*; D051616:Neuronal Apoptosis-Inhibitory Protein / Q000096:biosynthesis*; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D051381:Rats; D043683:Receptors, Adenosine A2 / Q000378:metabolism; D013091:Spermatogenesis / Q000187:drug effects; D000077022:Survivin; D013737:Testis / Q000378:metabolism* / Q000473:pathology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology; D014646:Varicocele / Q000378:metabolism* / Q000473:pathology
D058917:Adenosine A2 Receptor Antagonists; C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; C496803:Naip6 protein, rat; D051616:Neuronal Apoptosis-Inhibitory Protein; D009838:Oligodeoxyribonucleotides; D043683:Receptors, Adenosine A2; D000077022:Survivin; C057837:3,7-dimethyl-1-propargylxanthine; D013805:Theobromine