× Spermatogenesis is a process that takes place in the testis and is regulated by the hypothalamus-pituitary axis through the release of the pituitary gonadotropins FSH and LH. However, this process can be regulated also by local factors through autocrine and paracrine mechanisms. Among the molecules that act in the testis, there are PACAP (Pituitary Adenylate Cylcase-Activating Polypeptide), whose testicular concentration exceeds that of any other peptide, and VIP (Vasoactive Intestinal Peptide) (Li and Arimura, 2003), two neuropeptides belonging to the superfamily PACAP/glucagon/secretin, which includes also glucagon, GLP-1 (glucagon-Like-Peptide-1), GLP-2, GIP (Glucose-Dependent-insulinotropic polypeptide), GHRH (GH-Releasing Hormone), PHM (Peptide Histidine-Methionine) and secretin; they share the structure, distribution, functions and common receptors (Sherwood et al., 2000). PACAP is the member of the superfamily discovered by Miyata and his staff in 1989 from ovine hypothalamic extracts based on its ability to stimulate the cAMP formation in rat anterior pituitary cells; this neuropeptide exists in two different forms, PACAP27 and PACAP38, of 27 and 38 amino acids, respectively. Within this superfamily, the PACAP is of particular interest because its nucleotide and amino acid sequences are highly conserved in vertebrates, thus suggesting that its functions are essential for survival. Indeed, this neuropeptide is involved in multiple functions, such as the release of neurotransmitters, vasodilation, intestinal motility, secretion of insulin and histamine, proliferation and/or cell differentiation, induction and/or protection from apoptosis and reproduction (Vaudry et al., 2009; Vaudry et al., 2000). In the gonads, in particular in the testis, PACAP levels are higher than those of whole brain (Arimura et al., 1991), thus suggesting that PACAP is a molecule involved in the spermatogenesis control. VIP, that is the first member of the PACAP/glucagon/secretin superfamily to be isolated (Said and Mutt, 1970a, b), is a 28 ammino acid peptide; as PACAP, it has a sequence highly conserved during evolution; it is involved in different functions, as it acts as a neuromodulator, it is involved in the nervous control of cardiovascular, respiratory and gastro-intestinal functions, and in the release of PRL, LH and GH - 5 - from the pituitary. Moreover, VIP, as PACAP, is well represented within the gonads (Sherwood et al ., 2000; Csaba et al ., 1997). The role of both neuropeptides in the spermatogenesis control has to be clarified; anyway, the informations are available especially in mammals (Heindel et., 1992; Shioda et al., 1994; Romanelli et al., 1997; El- Gehani et al., 1998a, b, c; El- Gehani et al., 2000; Tanii et al., 2011; Nakamure et al., 2013). In non-mammalian vertebrates the investigations are still limited to a few species including the amphibian Triturus carnifex (Gobbetti and Zerani, 2002), the cartilaginous fish Torpedo marmorata (Agnese et al., 2013; Agnese et al., 2012) and the lizard Podarcis sicula; in such a species, Agnese et al. (2010) have shown that during the reproductive period PACAP and PAC1 receptor are widely distributed in both germ and somatic cells, thus suggesting a possible role of PACAP in the control of Podarcis sicula spermatogenesis. The aim of this PhD thesis is to determine the role of PACAP and VIP in the spermatogenesis of Podarcis sicula, the most common Italian reptile; the male of Podarcis sicula is a seasonal breeder, in which the various stages of spermatogenesis (mitotic, meiotic and differentiative phases) are naturally separated (Angelini and Botte, 1992). The investigation was carried out following two research lines: the first one evaluates the testicular expression/distribution of PACAP, VIP and their receptors in the different periods of the reproductive cyle; the second line studies the effects on spermatogenesis induced by PACAP, VIP and their receptors antagonists. I demonstrated that both neuropeptides are widely distributed in testis in all periods of reproductive Podarcis sicula cycle, and that they are involved in the control of testosterone and 17β-estradiol synthesis.