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Reprod Biol Endocrinol. 2018 Jun 23;16(1):62. doi: 10.1186/s12958-018-0375-5.

Melatonin inhibits 17β-estradiol-induced migration, invasion and epithelial-mesenchymal transition in normal and endometriotic endometrial epithelial cells.

Qi S1,2,3, Yan L1,2,3, Liu Z4, Mu YL5, Li M5, Zhao X5, Chen ZJ1,2,3,6,7, Zhang H8.

Author information

1
Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250021, People's Republic of China.
2
National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, 250021, People's Republic of China.
3
The Key laboratory for Reproductive Endocrinology, Shandong University, Ministry of Education, Jinan, 250021, People's Republic of China.
4
Department of Urology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, 250012, People's Republic of China.
5
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China.
6
Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai, 200030, People's Republic of China.
7
Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, People's Republic of China.
8
Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong University, 324 Jingwu Road, Jinan, 250021, People's Republic of China. huizhang1218@126.com.

Abstract

BACKGROUND:

Melatonin is a potential therapeutic agent for endometriosis, but its molecular mechanism is unclear. Here, we investigated the effect of melatonin on the epithelial-mesenchymal transition (EMT) in endometriotic endometrial epithelial cells and explored the pathway that might be involved.

METHODS:

This hospital-based study included 60 women of reproductive age using the endometrium for immunohistochemistry, 6 women of reproductive age undergoing bilateral tubal ligation and 6 patients with endometriosis for isolation of endometrial epithelial cells or subsequent analysis, respectively. We examined the expression of Notch1/Numb signaling and EMT markers by immunohistochemistry analysis and western blot analysis, the invasion and migration of endometrial epithelial cells by transwell assays, and the cell proliferation by CCK8 assays.

RESULTS:

Compared with normal endometrium, the endometriotic eutopic endometrium showed increased expression of Notch1, Slug, Snail, and N-cadherin, and decreased expression of E-cadherin and Numb. Melatonin or Notch inhibition by specific inhibitor blocked 17β-estradiol-induced cell proliferation, invasion, migration and EMT-related markers in both normal and endometriotic epithelial cells.

CONCLUSIONS:

Our data suggest that aberrant expression of Notch1/Numb signaling and the EMT is present in endometriotic endometrium. Melatonin may block 17β-estradiol-induced migration, invasion and EMT in normal and endometriotic epithelial cells by upregulating Numb expression and decreasing the activity of the Notch signaling pathway.

KEYWORDS:

17β-estradiol; Endometrial epithelial cells; Epithelial-mesenchymal transition; Melatonin; Migration and invasion

PMID:
29935526
PMCID:
PMC6015458
DOI:
10.1186/s12958-018-0375-5
[Indexed for MEDLINE]
Free PMC Article

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