Abstract
Cadmium (Cd) impairs the blood-testis barrier (BTB) with changes of its junctional complexes [1]. Polydeoxyribonucleotide (PDRN), an adenosine A2A agonist, has positive effects on male reproductive system [2]. We investigated the effects of PDRN on the morphological and functional Cd-induced changes in mice testes. Swiss mice were divided into four groups: control animals treated with 0.9% NaCl (1 ml/kg, i.p., daily); control animals treated 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 and treated with PDRN. The experiments lasted 14 days. At the end of experiment, the testes were processed for biochemical, structural and ultrastructural evaluation. CdCl2 increased pERK 1/2 expression and Follicle Stimulating Hormone (FSH) and Luteinizing Hormone (LH) levels, decreased testosterone (TE) and inhibin-B levels and induced structural damages in the extratubular compartment and in the seminiferous epithelium, with ultrastructural features of BTB disruption. Many TUNEL-positive germ cells were present in the peripheral parts of the tubules. CdCl2 increased also tubular TGF-β3 immunoreactivity and reduced claudin-11, occludin and N-cadherin immunoreactivity. PDRN administration reduced pERK 1/2 expression, FSH and LH levels, increased TE and inhibin-B levels, ameliorated germinal epithelium changes and protected BTB ultrastructure. Only few TUNEL-positive germ cells were present and the extratubular compartment was preserved, showing only a mild edema. Furthermore PDRN decreased TGF-β3 immunoreactivity and enhanced claudin-11, occludin and N-cadherin immunoreactivity. We demonstrate, for the first time, a protective effect of PDRN on Cd-induced BTB damages in mice testes. We suggest that the A2A agonist may play an important role against environmental Cd, and in particular against its harmful effects on gametogenesis.
