From Fertilisation to Implantation in Mammalian Pregnancy-Modulation of Early Human Reproduction by the Endocannabinoid System

Overview

Journal Pharmaceuticals (Basel)

Publisher MDPI

Specialty Chemistry

Date 2016 Oct 8

PMID 27713383

Citations 6

Authors

Katerina N Bambang

Tulay Karasu

Alpha Gebeh

Anthony H Taylor

Timothy H Marczylo

Patricia Lam

Jonathon M Willets

Justin C Konje

Affiliations

Soon will be listed here.

Abstract

There is an increasing recognition that the endocannabinoid system is the crucial cytokine-hormone system regulating early human pregnancy. The synchronous development of the fertilized embryo and the endometrium to ensure timely implantation has been shown to be one of the pivotal steps to successful implantation. This development is thought to be regulated by a finely balanced relationship between various components of the endocannabinoid system in the endometrium, the embryo and the Fallopian tube. In addition, this system has also been shown to be involved in the regulation of the development and maturation of the gametes prior to fertilization. In this review, we will examine the evidence from animal and human studies to support the role of the endocannabinoid system in gametogenesis, fertilization, implantation, early pregnancy maintenance, and in immunomodulation of pregnancy. We will discuss the role of the cannabinoid receptors and the enzymes involved in the synthesis and degradation of the key endocannabinoid ligands (e.g., anandamide and 2-arachinoylglycerol) in early reproduction.

Citing Articles

Association between serum antibody levels and infertility among reproductive-aged women in the U.S.

Li P, Chen Z Front Public Health. 2023; 11:1117245.

PMID: 37089503 PMC: 10113615. DOI: 10.3389/fpubh.2023.1117245.

Nitric oxide positively affects endometrial receptivity via FAAH and NAPE-PLD .

Melford S, Taylor A, Konje J Reprod Fertil. 2022; 2(2):107-116.

PMID: 35128447 PMC: 8812446. DOI: 10.1530/RAF-20-0035.

(Endo)Cannabinoids and Gynaecological Cancers.

Taylor A, Tortolani D, Ayakannu T, Konje J, Maccarrone M Cancers (Basel). 2020; 13(1).

PMID: 33375539 PMC: 7795647. DOI: 10.3390/cancers13010037.

New Insights of Uterine Leiomyoma Pathogenesis: Endocannabinoid System.

Ayakannu T, Taylor A, Marczylo T, Konje J Med Sci Monit Basic Res. 2019; 25:76-87.

PMID: 30842391 PMC: 6421936. DOI: 10.12659/MSMBR.914019.

Variation in stability of endogenous reference genes in fallopian tubes and endometrium from healthy and ectopic pregnant women.

Gebeh A, Marczylo E, Amoako A, Willets J, Konje J Int J Mol Sci. 2012; 13(3):2810-2826.

PMID: 22489127 PMC: 3317689. DOI: 10.3390/ijms13032810.

References

Maccarrone M, Cecconi S, Rossi G, Battista N, Pauselli R, Finazzi-Agro A . Anandamide activity and degradation are regulated by early postnatal aging and follicle-stimulating hormone in mouse Sertoli cells. Endocrinology. 2002; 144(1):20-8. DOI: 10.1210/en.2002-220544. View

Wang H, Dey S . Roadmap to embryo implantation: clues from mouse models. Nat Rev Genet. 2006; 7(3):185-99. DOI: 10.1038/nrg1808. View

Pestonjamasp V, Burstein S . Anandamide synthesis is induced by arachidonate mobilizing agonists in cells of the immune system. Biochim Biophys Acta. 1998; 1394(2-3):249-60. DOI: 10.1016/s0005-2760(98)00110-6. View

Ross R, Brockie H, Pertwee R . Inhibition of nitric oxide production in RAW264.7 macrophages by cannabinoids and palmitoylethanolamide. Eur J Pharmacol. 2000; 401(2):121-30. DOI: 10.1016/s0014-2999(00)00437-4. View

Wang H, Matsumoto H, Guo Y, Paria B, Roberts R, Dey S . Differential G protein-coupled cannabinoid receptor signaling by anandamide directs blastocyst activation for implantation. Proc Natl Acad Sci U S A. 2003; 100(25):14914-9. PMC: 299852. DOI: 10.1073/pnas.2436379100. View

Wei B, Mikkelsen T, McKinney M, Lander E, Cravatt B . A second fatty acid amide hydrolase with variable distribution among placental mammals. J Biol Chem. 2006; 281(48):36569-78. DOI: 10.1074/jbc.M606646200. View

Park B, McPartland J, Glass M . Cannabis, cannabinoids and reproduction. Prostaglandins Leukot Essent Fatty Acids. 2003; 70(2):189-97. DOI: 10.1016/j.plefa.2003.04.007. View

Jin X, Uyama T, Wang J, Okamoto Y, Tonai T, Ueda N . cDNA cloning and characterization of human and mouse Ca(2+)-independent phosphatidylethanolamine N-acyltransferases. Biochim Biophys Acta. 2008; 1791(1):32-8. DOI: 10.1016/j.bbalip.2008.09.006. View

Muccioli G . Endocannabinoid biosynthesis and inactivation, from simple to complex. Drug Discov Today. 2010; 15(11-12):474-83. DOI: 10.1016/j.drudis.2010.03.007. View

10.

Idris A, van t Hof R, Greig I, Ridge S, Baker D, Ross R . Regulation of bone mass, bone loss and osteoclast activity by cannabinoid receptors. Nat Med. 2005; 11(7):774-9. PMC: 1430341. DOI: 10.1038/nm1255. View

11.

Piccinni M . T-cell cytokines in pregnancy. Am J Reprod Immunol. 2002; 47(5):289-94. DOI: 10.1034/j.1600-0897.2002.01104.x. View

12.

Larque E, Krauss-Etschmann S, Campoy C, Hartl D, Linde J, Klingler M . Docosahexaenoic acid supply in pregnancy affects placental expression of fatty acid transport proteins. Am J Clin Nutr. 2006; 84(4):853-61. DOI: 10.1093/ajcn/84.4.853. View

13.

Fonseca B, Correia-da-Silva G, Taylor A, Lam P, Marczylo T, Konje J . N-acylethanolamine levels and expression of their metabolizing enzymes during pregnancy. Endocrinology. 2010; 151(8):3965-74. DOI: 10.1210/en.2009-1424. View

14.

Furuhashi M, Hotamisligil G . Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008; 7(6):489-503. PMC: 2821027. DOI: 10.1038/nrd2589. View

15.

Mechoulam R, Deutsch D . Toward an anandamide transporter. Proc Natl Acad Sci U S A. 2005; 102(49):17541-2. PMC: 1308911. DOI: 10.1073/pnas.0508644102. View

16.

Maccarrone M, Bisogno T, Valensise H, Lazzarin N, Fezza F, Manna C . Low fatty acid amide hydrolase and high anandamide levels are associated with failure to achieve an ongoing pregnancy after IVF and embryo transfer. Mol Hum Reprod. 2002; 8(2):188-95. DOI: 10.1093/molehr/8.2.188. View

17.

El-Talatini M, Taylor A, Elson J, Brown L, Davidson A, Konje J . Localisation and function of the endocannabinoid system in the human ovary. PLoS One. 2009; 4(2):e4579. PMC: 2640464. DOI: 10.1371/journal.pone.0004579. View

18.

Habayeb O, Bell S, Konje J . Endogenous cannabinoids: metabolism and their role in reproduction. Life Sci. 2002; 70(17):1963-77. DOI: 10.1016/s0024-3205(01)01539-9. View

19.

Maccarrone M, Valensise H, Bari M, Lazzarin N, Romanini C, Finazzi-Agro A . Progesterone up-regulates anandamide hydrolase in human lymphocytes: role of cytokines and implications for fertility. J Immunol. 2001; 166(12):7183-9. DOI: 10.4049/jimmunol.166.12.7183. View

20.

Maccarrone M, Valensise H, Bari M, Lazzarin N, Romanini C, Finazzi-Agro A . Relation between decreased anandamide hydrolase concentrations in human lymphocytes and miscarriage. Lancet. 2000; 355(9212):1326-9. DOI: 10.1016/S0140-6736(00)02115-2. View