{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:25:00Z","timestamp":1783686300257,"version":"3.55.0"},"reference-count":62,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T00:00:00Z","timestamp":1745366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endocannabinoid system (ECS) is a complex endocrine network involved in maintaining body homeostasis. It comprises endocannabinoids, their receptors (CB1 and CB2), and the enzymes and transporters responsible for their synthesis and degradation. While the ECS\u2019s role in the nervous system is well established, its functions in other organs and peripheral tissues, including the cardiovascular, gastrointestinal, and reproductive systems, remain incompletely understood. With the increasing use of marijuana, particularly among individuals of reproductive age, concerns have emerged regarding its potential impact on male and female fertility. Phytocannabinoids (\u22069tethrahydrocannabinol and cannabidiol), as well as synthetic cannabimimetic drugs, interact with the ECS, influencing sperm and oocyte physiology and reproductive outcomes. Recent research has identified ECS-related biomarkers with potential applications in infertility diagnosis, particularly in assessing male fertility with greater precision. Furthermore, emerging evidence suggests that ECS signaling pathways are involved in epigenetic modifications, which may influence health maintenance, disease susceptibility, and transgenerational inheritance patterns. These findings highlight the therapeutic potential of ECS modulation in reproductive disorders and broader medical applications. This narrative review aims to elucidate the role of the ECS in human reproduction, with a particular focus on the influence of endocannabinoids on gametogenesis. While current research underscores the critical role of the ECS in fertility, further investigations are needed to fully elucidate its underlying mechanisms and its broader implications for reproductive health and therapeutic interventions.<\/jats:p>","DOI":"10.3390\/ijms26093996","type":"journal-article","created":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T10:40:48Z","timestamp":1745404848000},"page":"3996","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of the Endocannabinoid System in Human Gametogenesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3559-0947","authenticated-orcid":false,"given":"Nina","family":"Montik","sequence":"first","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniele","family":"Crescenzi","sequence":"additional","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Marzocchini","sequence":"additional","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Lubinski","sequence":"additional","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Grementieri","sequence":"additional","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Peruzzi","sequence":"additional","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2042-798X","authenticated-orcid":false,"given":"Marta","family":"Lomb\u00f3","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology, Universidad de Le\u00f3n, 24071 Le\u00f3n, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8037-4947","authenticated-orcid":false,"given":"Andrea","family":"Ciavattini","sequence":"additional","affiliation":[{"name":"Gynecologic Section, Department of Odontostomatologic and Specialized Clinical Sciences, Universit\u00e0 Politecnica delle Marche, 60123 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5994-0572","authenticated-orcid":false,"given":"Oliana","family":"Carnevali","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Sciences, Polytechnic University of Marche, 60131 Ancona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1152\/physrev.00002.2016","article-title":"Pleiotropic Physiological and Pathological Roles Through Complex Pharmacology","volume":"96","author":"Ligresti","year":"2016","journal-title":"Physiol. 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