{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T20:25:40Z","timestamp":1791318340820,"version":"4.3.1"},"reference-count":285,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T00:00:00Z","timestamp":1753228800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Wroc\u0142aw University of Environmental and Life Sciences"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endocannabinoid system (ECS) is a complex neuromodulatory network involved in maintaining physiological balance through interactions with various neurotransmitter and hormonal pathways. Its key components\u2014cannabinoid receptors (CBRs)\u2014are activated by endogenous ligands and exogenous cannabinoids such as those found in the Cannabis sativa plant. Although cannabinoids like cannabidiol (CBD) have garnered interest for their potential therapeutic effects, evidence regarding their safety, particularly for reproductive health, remains limited. This review summarizes the structure and molecular mechanisms of the ECS, its role in reproductive physiology\u2014including its interactions with the hypothalamic\u2013pituitary\u2013gonadal axis (HPG axis), gametogenesis, implantation, and lactation\u2014and the possible consequences of cannabinoid exposure for fertility. In addition, we focus on the involvement of the ECS and cannabinoids in breast cancer, highlighting emerging evidence on their dual role in tumor progression and therapy. These insights emphasize the need for further research to better define the therapeutic potential and risks associated with cannabinoid use in reproductive health and breast cancer.<\/jats:p>","DOI":"10.3390\/ijms26157095","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T14:22:44Z","timestamp":1753280564000},"page":"7095","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular Mechanisms of the Endocannabinoid System with a Focus on Reproductive Physiology and the Cannabinoid Impact on Fertility"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4927-095X","authenticated-orcid":false,"given":"Patrycja","family":"Kalak","sequence":"first","affiliation":[{"name":"Department of Reproduction and Farm Animals, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1264-7050","authenticated-orcid":false,"given":"Piotr","family":"Kupczyk","sequence":"additional","affiliation":[{"name":"Department of General and Experimental Pathology, Wroclaw Medical University, 50-368 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9058-1598","authenticated-orcid":false,"given":"Antoni","family":"Szumny","sequence":"additional","affiliation":[{"name":"Department of Food Chemistry and Biocatalysis, Faculty of Biotechnology and Food Science, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8742-0790","authenticated-orcid":false,"given":"Tomasz","family":"G\u0119barowski","sequence":"additional","affiliation":[{"name":"Department of Animal Physiology and Biostructure, Faculty of Veterinary Medicine, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Jasiak","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases with Clinic for Horses, Dogs, and Cats, Wroclaw University of Environmental and Life Sciences, pl. Grunwaldzki 47, 50-366 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8925-4853","authenticated-orcid":false,"given":"Artur","family":"Nied\u017awied\u017a","sequence":"additional","affiliation":[{"name":"Department of Internal Diseases with Clinic for Horses, Dogs, and Cats, Wroclaw University of Environmental and Life Sciences, pl. Grunwaldzki 47, 50-366 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1056-0784","authenticated-orcid":false,"given":"Wojciech","family":"Ni\u017ca\u0144ski","sequence":"additional","affiliation":[{"name":"Department of Reproduction and Farm Animals, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5063-4306","authenticated-orcid":false,"given":"Micha\u0142","family":"Dzi\u0119cio\u0142","sequence":"additional","affiliation":[{"name":"Department of Reproduction and Farm Animals, Wroclaw University of Environmental and Life Sciences, 50-375 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/cbdv.200790144","article-title":"History of Cannabis and Its Preparations in Saga, Science, and Sobriquet","volume":"4","author":"Russo","year":"2007","journal-title":"Chem. 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