The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary
Objective(s): Cannabinoids, derivatives of Cannabis sativa L., can activate the endocannabinoid system via two endogenous receptors, CB1 and CB2. This system is crucial in regulating folliculogenesis, fertility, and reproductive function. This study investigated the potential effects of cannabinoid...
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| Format: | Article |
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Mashhad University of Medical Sciences
2025-09-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_26077_ec54d238ae704d2003d389617078ce2b.pdf |
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| author | Vida Mirzaie Touba Eslaminejad Fatemeh Sheikhbahaei Shayan Vafaei Fatemeh Nabipour Mina Behzadi Seyyed Noureddin Nematollahi-Mahani |
| author_facet | Vida Mirzaie Touba Eslaminejad Fatemeh Sheikhbahaei Shayan Vafaei Fatemeh Nabipour Mina Behzadi Seyyed Noureddin Nematollahi-Mahani |
| author_sort | Vida Mirzaie |
| collection | DOAJ |
| description | Objective(s): Cannabinoids, derivatives of Cannabis sativa L., can activate the endocannabinoid system via two endogenous receptors, CB1 and CB2. This system is crucial in regulating folliculogenesis, fertility, and reproductive function. This study investigated the potential effects of cannabinoid agonists and antagonists on ovarian health and function in female mice.Materials and Methods: 80 NMRI mice were divided into 10 groups. Treatment groups received CB1 or CB2 agonists, antagonists, or their combinations for five days. The animals were then sacrificed, the ovaries were excised and weighed, and their volume was measured. Total RNA was extracted from the left ovary for qPCR analysis, while the right ovary was fixed in Bouin’s solution for histological evaluation following H&E staining.Results: Treatment with CB1/CB2 agonist+CB1 antagonist (W102+AM251) decreased the level of NAPE-PLD (a key factor in the production of endocannabinoids in cells) and increased the level of FAAH (responsible for cannabinoid degradation) genes compared to all groups. CB2 antagonist (AM630) increased the number of primary, preantral, and antral follicles, the volume and weight of ovaries, and estrogen levels. Meanwhile, the CB1 antagonist (AM251) significantly increased microvascular density in the ovaries.Conclusion: Cannabinoids modulate ovarian physiology and folliculogenesis, with CB2 receptors playing a particularly significant role. Antagonism at CB2 appeared to differentially affect cannabinoid-metabolizing enzymes in ovarian follicles and differentially affect their maturation. However, our preliminary novel findings in mice require human studies before clinical application. |
| format | Article |
| id | doaj-art-cad1fa66504648cba7c4b193fc555577 |
| institution | Kabale University |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-cad1fa66504648cba7c4b193fc5555772025-08-20T03:35:48ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-09-012891171117910.22038/ijbms.2025.85417.1846826077The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovaryVida Mirzaie0Touba Eslaminejad1Fatemeh Sheikhbahaei2Shayan Vafaei3Fatemeh Nabipour4Mina Behzadi5Seyyed Noureddin Nematollahi-Mahani6Department of Anatomical Science, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, IranDepartment of Anatomical Science, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, IranDepartment of Anatomical Science, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, IranDepartment of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pathology, School of Medicine, Kerman University of Medical Sciences, Kerman, IranKerman Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, IranDepartment of Anatomical Science, Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, IranObjective(s): Cannabinoids, derivatives of Cannabis sativa L., can activate the endocannabinoid system via two endogenous receptors, CB1 and CB2. This system is crucial in regulating folliculogenesis, fertility, and reproductive function. This study investigated the potential effects of cannabinoid agonists and antagonists on ovarian health and function in female mice.Materials and Methods: 80 NMRI mice were divided into 10 groups. Treatment groups received CB1 or CB2 agonists, antagonists, or their combinations for five days. The animals were then sacrificed, the ovaries were excised and weighed, and their volume was measured. Total RNA was extracted from the left ovary for qPCR analysis, while the right ovary was fixed in Bouin’s solution for histological evaluation following H&E staining.Results: Treatment with CB1/CB2 agonist+CB1 antagonist (W102+AM251) decreased the level of NAPE-PLD (a key factor in the production of endocannabinoids in cells) and increased the level of FAAH (responsible for cannabinoid degradation) genes compared to all groups. CB2 antagonist (AM630) increased the number of primary, preantral, and antral follicles, the volume and weight of ovaries, and estrogen levels. Meanwhile, the CB1 antagonist (AM251) significantly increased microvascular density in the ovaries.Conclusion: Cannabinoids modulate ovarian physiology and folliculogenesis, with CB2 receptors playing a particularly significant role. Antagonism at CB2 appeared to differentially affect cannabinoid-metabolizing enzymes in ovarian follicles and differentially affect their maturation. However, our preliminary novel findings in mice require human studies before clinical application.https://ijbms.mums.ac.ir/article_26077_ec54d238ae704d2003d389617078ce2b.pdfcannabinoidcannabinoid agonistcannabinoid antagonistcb1 receptorcb2 receptorfolliculogenesis |
| spellingShingle | Vida Mirzaie Touba Eslaminejad Fatemeh Sheikhbahaei Shayan Vafaei Fatemeh Nabipour Mina Behzadi Seyyed Noureddin Nematollahi-Mahani The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary Iranian Journal of Basic Medical Sciences cannabinoid cannabinoid agonist cannabinoid antagonist cb1 receptor cb2 receptor folliculogenesis |
| title | The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary |
| title_full | The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary |
| title_fullStr | The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary |
| title_full_unstemmed | The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary |
| title_short | The role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary |
| title_sort | role of cannabinoid agonists and antagonists on folliculogenesis and evolutionary events in the mouse ovary |
| topic | cannabinoid cannabinoid agonist cannabinoid antagonist cb1 receptor cb2 receptor folliculogenesis |
| url | https://ijbms.mums.ac.ir/article_26077_ec54d238ae704d2003d389617078ce2b.pdf |
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