Cannabinoids and Reproduction: A Lasting and Intriguing History

Abstract

Starting from an historical overview of lasting Cannabis use over the centuries, we will focus on a description of the cannabinergic system, with a comprehensive analysis of chemical and pharmacological properties of endogenous and synthetic cannabimimetic analogues. The metabolic pathways and the signal transduction mechanisms, activated by cannabinoid receptors stimulation, will also be discussed. In particular, we will point out the action of cannabinoids and endocannabinoids on the different neuronal networks involved in reproductive axis, and locally, on male and female reproductive tracts, by emphasizing the pivotal role played by this system in the control of fertility.

An Assessment of the Genotoxicity and Subchronic Toxicity of a Supercritical Fluid Extract of the Aerial Parts of Hemp

“…Cannabinoids are chiefly known to act on the cannabinoid receptors CB1 and CB2 (as well as transient potential vanilloid channel type 1 receptors) [8, 9]. CB1 receptors are primarily found in the central nervous system but are also found in peripheral tissues, including those of the pituitary gland, gastrointestinal system, reproductive system, and immune system [8, 10].…”

“…CB1 receptors are primarily found in the central nervous system but are also found in peripheral tissues, including those of the pituitary gland, gastrointestinal system, reproductive system, and immune system [8, 10]. CB2 receptors are found in the central nervous system (e.g., neuronal microglia cells, brain stem cells, and cerebellum) as well as peripherally in tissues such as the spleen, thymus, tonsils, mast cells, and reproductive system [8, 11, 12]. …”

Low 17beta-Estradiol Levels in Cnr1 Knock-Out Mice Affect Spermatid Chromatin Remodeling by Interfering with Chromatin Reorganization

“…Endocannabinoids regulate reproduction in male and female [6,[11][12][13][14] and they have been identified as actors in the intricate process of spermiogenesis [15]. In male, they act, directly and/or indirectly, at both central (hypothalamus and hypophysis) [16][17][18] and local levels (testis, epididymis and deferent ducts) via their cognate receptors [19][20][21][22][23][24][25][26].…”

“…At the testicular level, endocannabinoids affect both spermatogenesis and steroidogenesis. In rodents, they regulate immature Sertoli cell activity [28], promote meiosis (i.e., spermatogonia-to-spermatocyte progression) [23], support adult Leydig cell development [29] and function [30] as well as SPT differentiation [14,22,31]. Indeed, in the absence of CNR1 activity, inadequate chromatin remodeling of SPT occurs.…”

Role of the Endocannabinoid System in the Central Regulation of Nonmammalian Vertebrate Reproduction

“…In vertebrates ECS modulates reproductive functions by acting at multiple levels (for a review, see [42]). Centrally, ECS negatively affects the secretion of pituitary gonadotropin hormones, by acting at the hypothalamic level.…”