Endocannabinoids affect the reproductive functions in teleosts and amphibians

Abstract

Following the discovery in the brain of the bonyfish Fugu rubripes of two genes encoding for type 1 cannabinoid receptors (CB1A and CB1B), investigations on the phylogeny of these receptors have indicated that the cannabinergic system is highly conserved. Among the multiple functions modulated by cannabinoids/endocannabinoids through the CB1 receptors one of the more investigated is the mammalian reproduction. Therefore, since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, the major aim of the present paper was to review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non mammalian vertebrates, namely bonyfish and amphibians.The expression and distribution of CB1 receptors were investigated in the CNS and gonads of two teleosts, Pelvicachromis pulcher and Carassius auratus as well as in the anuran amphibians Xenopus laevis and Rana esculenta. In general the large diffusion of neurons targeted by cannabinoids in both fish and amphibian forebrain indicate endocannabinoids as pivotal local messengers in several neural circuits involved in either sensory integrative activities, like the olfactory processes (in amphibians) and food response (in bonyfish), or neuroendocrine machinery (in both). By using immunohistochemistry for CB1 and GnRH, the codistribution of the two signalling molecules was found in the fish basal telencephalon and preoptic area, which are key centers for gonadotropic regulation in all vertebrates. A similar topographical codistribution was observed also in the septum of the telencephalon in Rana esculenta and Xenopus laevis.Interestingly, the double standard immunofluorescence on the same brain section, aided with a laser confocal microscope, showed that in anurans a subset of GnRH neurons exhibited also the CB1 immunostaining. The fact that CB1-LI-IR was found indeed in the FSH gonadotrophs of the Xenopus pituitary gland and CB1 receptors together with the fatty acid amide hydrolase, the degradative enzyme of the endocannabinoid anandamide, were demonstrated in both bonyfish and frog gonads, strongly suggests that endocannabinoids are involved in central and peripheral gonadotropic functions of teleosts and amphibians.

Endocannabinoids and Endovanilloids: A Possible Balance in the Regulation of the Testicular GnRH Signalling

“…The presence of cb1 in frog brain, mainly in the forebrain and midbrain—as also observed from fish to mammals [14, 41, 60, 61]—has suggested that eCS is able to control reproductive functions through a central regulation. This is in line with the discovery that hypothalamic immortalized GnRH secreting neurons possess a complete eCS, CB1 included [62] and that AEA inhibits GnRH release from rat mediobasal hypothalamus [63].…”

“…During the course of the years, the eCS has been characterized and studied from a functional point of view in many species [14–17]. In this regard, the use of nonmammalian animal models has contributed to a better comprehension about the eCS actions, especially in several reproductive events [16, 18–20].…”

Endocannabinoids and Kisspeptins: Two Modulators in Fight for the Regulation of GnRH Activity

“…The basal crosstalk between ECS and GnRH is evolutionarily conserved, since it has been described also in lower vertebrates (Chianese et al, , 2011bCottone et al, 2008. In both amphibians and teleost fish, CB1 was detected in the forebrain, the encephalic macro-area containing the anterior preoptic area, the encephalic region mainly involved in GnRH activity and in the control of gonadotropin discharge (Cottone et al, 2003Lam et al, 2006;Migliarini et al, 2006;Meccariello et al, 2008;Valenti et al, 2005).…”

“…In males, ECS modulates the progression of spermatogenesis, spermatozoa functions and the activity of testicular somatic cells in mammalian, non-mammalian vertebrates as well as in invertebrates. (Battista et al, 2012;Cacciola et al 2008;Cobellis et al, 2006;Cottone et al, 2008;Grimaldi et al, 2009;Maccarrone et al, 2003Maccarrone et al, , 2005Pierantoni et al, 2009, Schuel et al, 1991Wang et al, 2006). In females, ECBs represent fertility signals in folliculogenesis, follicle maturation, oocyte maturation and ovulation (El-Talatini et al, 2009).…”

Cannabinoid receptors are widely expressed in goldfish: molecular cloning of a CB2-like receptor and evaluation of CB1 and CB2 mRNA expression profiles in different organs

“…In zebrafish, on the other hand, only one CB1 gene has been detected (Lam et al 2006), while two CB2 genes (CB2A and CB2B) are present (Rodriguez-Martin et al 2007). In goldfish, a CB1 sequence has been cloned (Valenti et al 2005; Cottone et al 2005) and the distribution of the receptor has been analyzed in the retina (Yazulla et al 2000), CNS (Valenti et al 2005; Cottone et al 2005) and gonads (Cottone et al 2008). On the other hand, CB2 had not yet been identified in goldfish.…”