anandamide and Infertility--Female

Epidemiological studies have highlighted the ever growing use of illegal drugs among teenagers. The negative effects of marijuana (a Cannabis sativa extract) on reproductive health are poorly known among young people, although chronic exposure to delta-9-tetrahydrocannabinol, the main psychoactive constituent of marijuana, impairs human reproductive potential by disrupting menstrual cycle, suppressing oogenesis and impairing embryo implantation and development, in women, and by increasing ejaculation problems, reducing sperm count and motility, and generating loss of libido and impotence, in men. Endocannabinoids, their metabolic enzymes and target receptors form the so called "endocannabinoid system" and they have been demonstrated to respond to fertility signals. In addition, they interfere with hormones, cytokines and other signalling molecules in both female and male reproductive events. In this review, we shall summarize the current knowledge on the endocannabinoid system, and on the multifaceted roles played by endocannabinoids in reproduction along the evolutionary axis from invertebrates to mammals. Furthermore, we shall discuss the potential use of distinct elements of the endocannabinoid system for the diagnosis and/or treatment of human infertility.

Topics: Adolescent; Animals; Arachidonic Acids; Cannabinoid Receptor Modulators; Embryo Implantation; Endocannabinoids; Female; Fertility; Humans; Infertility, Female; Infertility, Male; Male; Polyunsaturated Alkamides; Pregnancy; Receptors, Cannabinoid; Reproduction; Signal Transduction

Although N-arachidonoylethanolamine (AEA; also known as anandamide) is present in human follicular fluid (FF), its regulation remains unknown. Therefore, the aims of the present study were to: (1) investigate the relationships between FF AEA concentrations in women undergoing assisted reproductive technology and their age, body mass index, ART characteristics and fertility treatment outcomes; and (2) assess how different inflammatory patterns may trigger AEA production by human granulosa cells (hGCs). FF AEA concentrations were higher in women undergoing IVF than in those undergoing intracytoplasmic sperm injection group. FF AEA median concentrations were lower in women undergoing ART because of male factor infertility than in women with endometriosis (1.6 vs 2.5nM respectively), but not women with tubal, hormonal or unexplained infertility (1.6, 2.4 and 1.9nM respectively). To evaluate the effects of macrophages on AEA production by hGCs, hGCs were cocultured with monocyte-derived macrophages. The conditioned medium from M1 polarised macrophages increased AEA production by hGCs. This was accompanied by an increase in AEA-metabolising enzymes, particularly N-acyl phosphatidylethanolamine-specific phospholipase D. The results of the present study show that high FF AEA concentrations in patients with endometriosis may be associated with the recruitment of inflammatory chemokines within the ovary, which together may contribute to the decreased reproductive potential of women with endometriosis. Collectively, these findings add a new player to the hormone and cytokine networks that regulate fertility in women.

Topics: Adolescent; Adult; Amidohydrolases; Arachidonic Acids; Case-Control Studies; Coculture Techniques; Cross-Sectional Studies; Endocannabinoids; Endometriosis; Female; Follicular Fluid; Granulosa Cells; Humans; Infertility, Female; Macrophages; Paracrine Communication; Phenotype; Phospholipase D; Polyunsaturated Alkamides; Prospective Studies; Reproductive Techniques, Assisted; THP-1 Cells; Young Adult

Polycystic ovary syndrome (PCOS) is a metabolic and endocrinal disorder affecting a number of women of reproductive age. We aimed to reveal the correlation between the endocannabinoid system and PCOS, which may provide a new therapeutic target for PCOS treatment.. Serum levels of anandamide and 2-arachidonoylglycerol andexpression of cannabinoid receptors and fatty acid amide hydrolase (FAAH) in the endometrium were compared between women with PCOS and infertile women without PCOS, as well as women with PCOS before and after treatment with Diane-35 and metformin. Cannabinoid receptors and FAAH in the endometrium were stained using the immunohistochemical method. Results were analyzed by calculating integrated optical density.. Plasma anandamide was increased significantly in women with PCOS compared with infertile women without PCOS. Treatment with Diane-35 and metformin reversed this increase in women with PCOS. No significant difference in 2-arachidonoylglycerol was observed between the infertile women with or without PCOS. The women with PCOS had lower endometrial expression of FAAH compared with infertile women without PCOS, whereas no significant difference in endometrial expression of cannabinoid receptors was observed between the women with PCOS and infertile women without PCOS. We found that after treatment with Diane-35 and metformin, FAAH expression tended toward a significant increase compared with women before the treatment.. Endocannabinoid system may be involved in the progression of PCOS, and serum anandamide could serve as a potential biomarker of clinical diagnosis of PCOS.

Topics: Adult; Amidohydrolases; Androgen Antagonists; Arachidonic Acids; Cyproterone Acetate; Drug Combinations; Endocannabinoids; Endometrium; Ethinyl Estradiol; Female; Glycerides; Humans; Infertility, Female; Metformin; Polycystic Ovary Syndrome; Polyunsaturated Alkamides; Receptors, Cannabinoid; Young Adult