Rosanna di Paola (University of Messina)| Livia Interdonato (University of Messina)| Tiziana Genovese (University of Messina)| Daniela Impellizzeri (University of Messina)| Salvatore Cuzzocrea (University of Messina)
Varicocele is an age-related disease with no current medical treatments positively acting on infertility. Toll-like receptor 4 (TLR4) expression is present in normal testis with an involvement in the immunological reactions. Peroxisome proliferator-activated receptor-α (PPAR-α) is a nuclear receptor whose role in fertility is still unclear. N-Palmitoylethanolamide (PEA), an emerging nutraceutical compound present in plants and animal foods, is an endogenous PPAR-α agonist with well-demonstrated anti-inflammatory and analgesics characteristics. In this model of mice varicocele, PPAR-α and TLR4 receptors role was investigated through the administration of ultra-micronized PEA (PEA-um). Male wild-type (WT), PPAR-α knockout (KO), and TLR4 KO mice were used. A group underwent sham operation and administration of vehicle or PEA-um (10mg/kg i.p.) for twenty-one days. Another group (WT, PPAR-α KO and TLR4 KO) underwent surgical varicocele and was treated with vehicle or PEA-um (10mg/kg i.p.) for twenty-one days. At the end of treatments, all animals were euthanized and both operated and contralateral testes were processed for histological and morphometric assessment, for PPAR-α, TLR4, occludin and claudin-11 immunohistochemistry and for PPAR-α, TLR4, TGF-β3, p-ERK 1/2 and NLRP3 Western Blot analysis. Collectively, our data showed that administration of PEA-um revealed a key role of PPAR-α and TLR4 in varicocele pathophysiology
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