Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2021

Open Access 01-12-2021 | Cannabinoid | Research

The cannabinoid receptor CB1 affects the proliferation and apoptosis of adenomyotic human uterine smooth muscle cells of the junctional zone: a mechanism study

Authors: Sha Wang, Bohan Li, Xue Shen, Hua Duan, Zhengchen Guo, Xiao Li, Fuqing Sun

Published in: Reproductive Biology and Endocrinology | Issue 1/2021

Login to get access

Abstract

Background

The denomyotic junctional zone (JZ) plays an important role in the pathogenesis of adenomyosis. Proliferating cell nuclear antigen (PCNA) is an important nuclear marker of cell proliferation. This study aimed to evaluate the effects of the cannabinoid receptor CB1 on proliferation and apoptosis in the JZ in women with and without adenomyosis.

Methods

JZ smooth muscle cells (JZSMCs) of the adenomyosis and control groups were collected and cultivated. Immunohistochemistry and immunoblotting were used for protein localization and expression detection of CB1 and PCNA. Additionally, qRT-PCR was used to quantitatively analyse the mRNA expression of the two. AM251 and ACEA were used to regulate the function of CB1 receptors, and CCK-8 assay and flow cytometry assay were used to verify the proliferation and apoptosis of JZSMCs after regulation.

Results

We demonstrated that in normal JZSMCs CB1 and PCNA messenger RNA (mRNA) and protein expression was significantly higher in the proliferative phase of the menstrual cycle than in the secretory phase. CB1 and PCNA expression in JZSMCs from women with ADS was significantly higher than that in control women and did not significantly differ across the menstrual cycle. CB1 receptor antagonist AM251 inhibited the proliferation of adenomyotic JZSMCs in a dose-dependent manner. The CB1 receptor agonist ACEA significantly promoted the proliferation of adenomyotic JZSMCs. The apoptosis rate of adenomyotic JZSMCs treated with AM251 was significantly higher than that of JZSMCs from the untreated control group. The apoptosis rate was significantly decreased in the ACEA group compared with that in the untreated control group. Furthermore, AM251 suppressed the phosphorylation of AKT and Erk1/2 in adenomyotic JZSMCs. The CB1 agonist ACEA significantly promoted the phosphorylation of AKT and Erk1/2.

Conclusions

Our results indicated that the levels of CB1 and PCNA were increased in patients with adenomyosis and that cyclic changes were lost. CB1 may affect uterine JZ proliferation and apoptosis in adenomyosis by enhancing AKT and MAPK/Erk signalling.
Literature
1.
Naftalin J, Hoo W, Pateman K, Mavrelos D, Holland T, Jurkovic D. How common is adenomyosis? A prospective study of prevalence using transvaginal ultrasound in a gynaecology clinic. Hum Reprod. 2012;27(12):3432–9.CrossRef
2.
Leyendecker G, Wildt L. A new concept of endometriosis and adenomyosis: tissue injury and repair (TIAR). Horm Mol Biol Clin Investig. 2011;5(2):125–42.PubMed
3.
Fusi L, Cloke B. Brosens.The uterine junctional zone. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):479–91.CrossRef
4.
Tamai K, Koyama T, Umeoka S, et al. Spectrum of MR features in adenomyosis. Best Pract Res Clin Obstet Gynaecol. 2006;20(4):583–602.CrossRef
5.
Zhang Y, Zhou L, Li TC, Duan Hua Yu, Pei, Wang HY. Ultrastructural features of endometrial-myometrial interface and its alteration in adenomyosis. Int J Clin Exp Pathol. 2014;7:1469–77.PubMedPubMedCentral
6.
Devane WA, Hanus L, Breuer A, et al. Isolation and structure of a brain constituent that binds to the cannabinoid receptor. Science. 1992;258:1946–9.CrossRef
7.
Balsevich G, Petrie GN, Hill MN. Endocannabinoids: Effectors of glucocorticoid signaling. FRONT NEUROENDOCRIN. 2017;47:86–108.CrossRef
8.
Lu H, Mackie K. An Introduction to the Endogenous Cannabinoid System. BIOL PSYCHIAT 2016, 79(7).
9.
Fraguas-Sánchez AI, Torres-Suárez AI. Medical Use of Cannabinoids Drugs. 2018;78(16):1665–703.PubMed
10.
Rapino C, Battista N, Bari M, Maccarrone M. Endocannabinoids as biomarkers of human reproduction. Human Reproduction Update. 2014;20(4):501–16.CrossRef
11.
El-Talatini MR, Taylor AH, Konje JC. The relationship between plasma levels of the endocannabinoid, anandamide, sex steroids, and gonadotrophins during the menstrual cycle. Fertil Steril. 2010;93(6):1989–96.CrossRef
12.
Schander JA, Correa F, Bariani MV, Blanco J, Cymeryng C, Jensen F, Wolfson ML, Franchi AM. A role for the endocannabinoid system in premature luteal regression and progesterone withdrawal in lipopolysaccharide-induced early pregnancy loss model[J]. Mol Hum Reprod. 2016;22(11):800–8.CrossRef
13.
Shen X, Duan H, Wang S, Hong W, Wang Y, Lin S. Expression of Cannabinoid Receptors in Myometrium and its Correlation With Dysmenorrhea in Adenomyosis. REPROD SCI. 2019;26(12):1618–25.CrossRef
14.
Asada H, Yamagata Y, Taketani T, et al. Potential link between estrogen receptor-alpha gene hypomethylation and uterine fibroid formation. Mol Hum Reprod. 2008;14(9):539–45.CrossRef
15.
Cuppoletti J, Malinowska DH, Chakrabarti J, Ueno R. Effects of lubiprostone on human uterine smooth muscle cells. Prostaglandins Other Lipid Mediat. 2008;86(14):56–60.CrossRef
16.
Tahara A, Tsukada J, Tomura Y, et al. Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells. Br J Pharmacol. 2000;129(1):131–9.CrossRef
17.
Lin J, Huo R, Xiao L, Zhu X, Xie J, Sun S, He Y, Zhang J, Sun Y, Zhou Z, Wu P, Shen B, Li D, Li N. A novel p53/microRNA-22/Cyr61 axis in synovial cells regulates inflammation in rheumatoid arthritis. Arthritis & Rheumatology (Hoboken, N.J.). 2014; 66(1): 49–59.
18.
Liu X, Nie J, Guo SW. Elevated immunoreactivity to tissue factor and its association with dysmenorrhea severity and the amount of menses in adenomyosis. Human reproduction (Oxford England). 2011;26(2):337–45.CrossRef
19.
Li J, Chung JPW, Wang S, Li T, Duan H. The Investigation and Management of Adenomyosis in Women Who Wish to Improve or Preserve Fertility. BIOMED RES INT. 2018;2018:1–12.
20.
Wang S, Duan H, Zhang Y. Abnormal activation of RhoA/ROCKI Signaling in junctional zone smooth muscle cells of patients. Reprod Sci. 2016;11(3):1011–9.
21.
Wang S, Duan H, Zhang Y, Sun FQ. Abnormal Activation of RhoA/ROCK-I Signaling in Junctional Zone Smooth Muscle Cells of Patients With Adenomyosis. REPROD SCI. 2015;23(3):333–41.CrossRef
22.
Iuvone T, De Filippis D, Di Spiezio Sardo A, D’Amico A, Simonetti S, Sparice S, Esposito G, Bifulco G, Insabato L, Nappi C, Guida M. Selective CB2 up-regulation in women affected by endometrial inflammation. Journal Of Cellular Molecular Medicine. 2008;12(2):661–70.CrossRef
23.
Dennedy D, Friel MC, Houlihan AM, Broderick DD, Smith VM, Morrison T. JJ. Cannabinoids and the human uterus during pregnancy. Am J Obstet Gynecol. 2004;190(1):2–9. discussion 3A.
24.
Sanchez A-M, Quattrone F, Pannese M, Ulisse A, Candiani M, Diaz-Alonso J, Velasco G, Panina-Bordignon P. The cannabinoid receptor CB1 contributes to the development of ectopic lesions in a mouse model of endometriosis. Hum Reprod. 2017;32(1):175–84.PubMed
25.
Han H, Liang X, Wang J, Zhao Q, Yang M, Rong W, Zhang G. Cannabinoid receptor 1 contributes to sprouted innervation in endometrial ectopic growth through mitogen-activated protein kinase activation. Brain Res. 2017;1663:132–40.CrossRef
26.
Gentilini D, Besana A, Vigano P, Dalino P, Vignali M, Melandri M, Busacca M, Di Blasio AM. Endocannabinoid system regulates migration of endometrial stromal cells via cannabinoid receptor 1 through the activation of PI3K and ERK1/2 pathways. Fertility Sterility. 2010;93(8):2588–93.CrossRef
27.
Cui N, Wang C, Zhao Z, Zhang J, Xu Y, Yang Y, Hao G. The Roles of Anandamide, Fatty Acid Amide Hydrolase, and Leukemia Inhibitory Factor on the Endometrium during the Implantation Window. Frontiers in Endocrinology. 2017;8:268.CrossRef
28.
Makker A, Goel MM, Das V, Agarwal A. PI3K-Akt-mTOR and MAPK signaling pathways in polycystic ovarian syndrome, uterine leiomyomas and endometriosis: an update. Gynecol Endocrinol. 2012;28(3):175–81.CrossRef
29.
Ngô C, Nicco C, Leconte M, Chéreau C, Arkwright S, Vacher-Lavenu M-C, Weill B, Chapron C, Batteux F. Protein kinase inhibitors can control the progression of endometriosis in vitro and in vivo. J Pathol. 2010;222(2):148–57.CrossRef
30.
Leconte M, Nicco C, Ngô C, Chéreau C, Chouzenoux S, Marut W, Guibourdenche J, Arkwright S, Weill B, Chapron C, Dousset B, Batteux F. The mTOR/AKT inhibitor temsirolimus prevents deep infiltrating endometriosis in mice. Am J Pathol. 2011;179(2):880–9.CrossRef
31.
McKinnon BD, Kocbek V, Nirgianakis K, Bersinger NA, Mueller MD. Kinase signalling pathways in endometriosis: potential targets for non-hormonal therapeutics. Human Reproduction Update. 2016;22(3):382–403.CrossRef
32.
Caunt CJ, Sale MJ, Smith PD, Cook SJ. MEK1 and MEK2 inhibitors and cancer therapy: the long and winding road[J]. Nature Reviews Cancer. 2015;15(10):577–92.CrossRef
33.
Gurbuz N, Asoglu MR, Ashour AA, Salama S, Kilic GS, Ozpolat B. A selective serotonin 5-HT1B receptor inhibition suppresses cells proliferation and induces apoptosis in human uterine leiomyoma cells. Eur J Obstet Gynecol Reprod Biol. 2016;206:114–9.CrossRef
Metadata
Title
The cannabinoid receptor CB1 affects the proliferation and apoptosis of adenomyotic human uterine smooth muscle cells of the junctional zone: a mechanism study
Authors
Sha Wang
Bohan Li
Xue Shen
Hua Duan
Zhengchen Guo
Xiao Li
Fuqing Sun
Publication date
01-12-2021
Publisher
BioMed Central
Keyword
Cannabinoid
Published in
Reproductive Biology and Endocrinology / Issue 1/2021
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-020-00690-0

Other articles of this Issue 1/2021

Reproductive Biology and Endocrinology 1/2021 Go to the issue

Research

Effect and mechanisms of reproductive tract infection on oxidative stress parameters, sperm DNA fragmentation, and semen quality in infertile males

Research

Effect of somatometric parameters on the prevalence and severity of varicocele: a systematic review and meta-analysis

Research

Evaluation of testicular glycogen storage, FGF21 and LDH expression and physiological parameters of sperm in hyperglycemic rats treated with hydroalcoholic extract of Securigera Securidaca seeds, and Glibenclamide

Research

Metformin reduces androgen receptor and upregulates homeobox A10 expression in uterine endometrium in women with polycystic ovary syndrome

Research

More blastocysts are produced from fewer oocytes in ICSI  compared to IVF – results from a sibling oocytes study and definition of a new key performance indicator

Research

HSF1 promotes endometriosis development and glycolysis by up-regulating PFKFB3 expression