The role of endocannabinoids in pregnancy
Authors:
Laštůvka Zdeněk 1; Suchopár Josef 2; Mašková Simona 1; Alblová Miroslava 1; Pařízek Antonín 1
Authors‘ workplace:
Gynekologicko-porodnická klinika 1. LF UK a VFN v Praze
1; DrugAgency, a. s., Praha
2
Published in:
Ceska Gynekol 2021; 86(5): 349-354
Category:
Review Article
doi:
https://doi.org/10.48095/cccg2021349
Overview
Objective: In this paper, we summarize the role of the endocannabinoid system in relation to pregnancy and childbirth and its potential for diagnosis of preterm birth. Methods: Review of articles in peer-reviewed journals using the PubMed database. Results: Endocannabinoid system plays a significant role in embryo development, transport and implantation as well as in placentation. It consists of numerous endogenous ligands; however, in relation to pregnancy there are mainly two studied representatives: anandamide and 2-arachidonoylglycerol. There is increasing evidence, in addition to early pregnancy events, that anandamide plays a regulatory role in pregnancy maintenance and the timing of labour. The activity of anandamide depends on its metabolic pathway and the enzymatic activity that ensures its conversion. Ultimately, changes in anandamide concentration lead to increased production of prostaglandins or prostamides, with inverse effects on pregnancy. The abuse of exogenous cannabinoids in pregnancy has substantial impact on the unborn child in many ways and may result in detrimental effects including preterm birth. Conclusion: Measuring anandamide concentration and the prostaglandin to prostamide ratio could be a useful tool in assessing the risk of preterm birth.
Keywords:
pregnancy – endocannabinoid system – labour
Sources
1. Hillard CJ. Circulating endocannabinoids: from whence do they come and where are they going? Neuropsychopharmacology 2018; 43 (1): 155–172. doi: 10.1038/npp.2017.130.
2. Devane W, Hanus L, Breuer A et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science 1992; 258 (5090): 1946–1949. doi: 10.1126/science.1470919.
3. Bowles NP, Karatsoreos IN, Li X et al. A peripheral endocannabinoid mechanism contributes to glucocorticoid-mediated metabolic syndrome. Proc Natl Acad Sci U S A 2015; 112 (1): 285–290. doi: 10.1073/pnas.1421420112.
4. Walker OS, Holloway AC, Raha S. The role of the endocannabinoid system in female reproductive tissues. J Ovarian Res 2019; 12 (1): 3. doi: 10.1186/s13048-018-0478-9.
5. Kumar A, Mishra AK, Singh V et al. Molecular and functional insights into Transient Receptor Potential Vanilloid 1 (TRPV1) in bull spermatozoa. Theriogenology 2019; 128: 207–217. doi: 10.1016/j.theriogenology.2019.01.029.
6. Chicca A, Marazzi J, Nicolussi S et al. Evidence for bidirectional endocannabinoid transport across cell membranes. J Biol Chem 2012; 287 (41): 34660–34682. doi: 10.1074/jbc.M112.373241.
7. Gellersen B, Brosens JJ. Cyclic decidualization of the human endometrium in reproductive health and failure. Endocr Rev 2014; 35 (6): 851–905. doi: 10.1210/er.2014-1045.
8. Fonseca BM, Cunha SC, Goncalves D et al. Decidual NK cell-derived conditioned medium from miscarriages affects endometrial stromal cell decidualisation: endocannabinoid anandamide and tumour necrosis factor-alpha crosstalk. Hum Reprod 2020; 35 (2): 265–274. doi: 10.1093/humrep/dez260.
9. Torella M, Bellini G, Punzo F et al. TNF-alpha effect on human delivery onset by CB1/TRPV1 crosstalk: new insights into endocannabinoid molecular signaling in preterm vs. term G. Analysis of the EC/EV pathway and predictive biomarkers for early diagnosis of preterm delivery. Minerva Ginecol 2019; 71 (5): 359–364. doi: 10.23736/S0026-4784.19.04405-8.
10. Wang H, Xie H, Sun X et al. Differential regulation of endocannabinoid synthesis and degradation in the uterus during embryo implantation. Prostaglandins Other Lipid Mediat 2007; 83 (1–2): 62–74. doi: 10.1016/j.prostaglandins.2006.09.009.
11. Cui N, Wang C, Zhao Z et al. The roles of anandamide, fatty acid amide hydrolase, and leukemia inhibitory factor on the endometrium during the implantation window. Front Endocrinol (Lausanne) 2017; 8: 268. doi: 10.3389/fendo.2017.00268.
12. Gebeh AK, Willets JM, Bari M et al. Elevated anandamide and related N-acylethanolamine levels occur in the peripheral blood of women with ectopic pregnancy and are mirrored by changes in peripheral fatty acid amide hydrolase activity. J Clin Endocrinol Metab 2013; 98 (3): 1226–1234. doi: 10.1210/jc.2012-3390.
13. Trabucco E, Acone G, Marenna A et al. Endocannabinoid system in first trimester placenta: low FAAH and high CB1 expression characterize spontaneous miscarriage. Placenta 2009; 30 (6): 516–522. doi: 10.1016/j.placenta.2009.03.015.
14. Taylor AH, Finney M, Lam PM et al. Modulation of the endocannabinoid system in viable and non-viable first trimester pregnancies by pregnancy-related hormones. Reprod Biol Endocrinol 2011; 9 (1): 152. doi: 10.1186/1477-7827-9-152.
15. Tong S, Ngian GL, Onwude JL et al. Diag-nostic accuracy of maternal serum macrophage inhibitory cytokine-1 and pregnancy-associated plasma protein-A at 6-10 weeks of gestation to predict miscarriage. Obstet Gynecol 2012; 119 (5): 1000–1008. doi: 10.1097/AOG.0b013e3182518fd3.
16. Almada M, Costa L, Fonseca B et al. The endocannabinoid 2-arachidonoylglycerol promotes endoplasmic reticulum stress in placental cells. Reproduction 2020; 160 (2): 171–180. doi: 10.1530/rep-19-0539.
17. Chamley LW, Bhalla A, Stone PR et al. Nuclear localisation of the endocannabinoid metabolizing enzyme fatty acid amide hydrolase (FAAH) in invasive trophoblasts and an association with recurrent miscarriage. Placenta 2008; 29 (11): 970–975. doi: 10.1016/j.placenta.2008.08.003.
18. Almada M, Oliveira A, Amaral C et al. Anandamide targets aromatase: a breakthrough on human decidualization. Biochim Biophys Acta Mol Cell Biol Lipids 2019; 1864 (12): 158512. doi: 10.1016/j.bbalip.2019.08.008.
19. Habayeb OM, Taylor AH, Bell SC et al. Expression of the endocannabinoid system in human first trimester placenta and its role in trophoblast proliferation. Endocrinology 2008; 149 (10): 5052–5060. doi: 10.1210/en.2007-1799.
20. Lam PM, Marczylo TH, El-Talatini M et al. Ultra performance liquid chromatography tandem mass spectrometry method for the measurement of anandamide in human plasma. Anal Biochem 2008; 380 (2): 195–201. doi: 10.1016/j.ab.2008.05.033.
21. Nallendran V, Lam PM, Marczylo TH et al. The plasma levels of the endocannabinoid, anandamide, increase with the induction of labour. BJOG 2010; 117 (7): 863–869. doi: 10.1111/j.1471-0528.2010.02555.x.
22. Ibsen MS, Connor M, Glass M. Cannabinoid CB (1) and CB (2) receptor signaling and bias. Cannabis Cannabinoid Res 2017; 2 (1): 48–60. doi: 10.1089/can.2016.0037.
23. Thompson R, DeJong K, Lo J. Marijuana use in pregnancy: a review. Obstet Gynecol Surv 2019; 74 (7): 415–428. doi: 10.1097/ogx.0000000 000000685.
24. Pollack R, Rana D, Purvis J et al. Effect of prenatal marijuana exposure on sleep wake cycles and amplitude-integrated electroencephalogram (aEEG). J Perinatol 2021; 41 (6): 1355–1363. doi: 10.1038/s41372-020-00911-9.
25. Cajachagua-Torres KN, Jaddoe VW, de Rijke YBet al. Parental cannabis and tobacco use during pregnancy and childhood hair cortisol concentrations. Drug Alcohol Depend 2021; 225: 108751. doi: 10.1016/j.drugalcdep.2021.108751.
26. Bandoli G, Jelliffe-Pawlowski L, Schumacher Bet al. Cannabis-related diagnosis in pregnancy and adverse maternal and infant outcomes. Drug Alcohol Depend 2021; 225: 108757. doi: 10.1016/j.drugalcdep.2021.108757.
27. Cao S, Jones M, Tooth L et al. Association between preconception cannabis use and risk of postpartum depression: findings from an Australian longitudinal cohort. Drug Alcohol Depend 2021; 226: 108860. doi: 10.1016/j.drugalcdep.2021.108860.
28. Kaarid KP, Vu N, Bartlett K et al. Assessing the prevalence and correlates of prenatal cannabis consumption in an urban Canadian population: a cross-sectional survey. CMAJ Open 2021; 9 (2): E703–E710. doi: 10.9778/cmajo.20200181.
29. Taylor DL, Bell JF, Adams SL et al. Factors associated with cannabis use during the reproductive cycle: a retrospective cross-sectional study of women in states with recreational and medical cannabis legalization. Matern Child Health J 2021; 25 (9): 1491–1500. doi: 10.1007/s10995-021-03197-1.
30. Bachkangi P, Taylor AH, Bari M et al. Prediction of preterm labour from a single blood test: the role of the endocannabinoid system in predicting preterm birth in high-risk women. Eur J Obstet Gynecol Reprod Biol 2019; 243: 1–6. doi: 10.1016/j.ejogrb.2019.09.029.
31. Chan HW, McKirdy NC, Peiris HN et al. The role of endocannabinoids in pregnancy. Reproduction 2013; 146 (3): R101–R109. doi: 10.1530/REP-12-0508.
Labels
Paediatric gynaecology Gynaecology and obstetrics Reproduction medicineArticle was published in
Czech Gynaecology
2021 Issue 5
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