Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells

Endometriosis, a common gynecological disorder characterized by the growth of endometrial gland and stroma outside the uterus, causes several symptoms such as dysmenorrhea, hypermenorrhea, and chronic abdominal pain. 17β estradiol (E2) stimulates the growth of endometriotic lesions. Although estetro...

Full description

Saved in:
Bibliographic Details
Published in:ENDOCRINE JOURNAL 2024, Vol.71(2), pp.199-206
Main Authors: Wakatsuki, Akihiko, Lin, Yinzhi, Kojima, Shiori, Matsushita, Hiroshi, Takeuchi, Kosei, Umezawa, Kazuo
Format: Article
Language:English
Subjects:
17β estradiol
Cell migration
Chronic pain
Down-regulation
Endometriosis
Endometrium
Estetrol
Estrogens
Fetuses
Immortalized human endometrial stromal cells
Lesions
Metastases
Oral contraceptives
Polymerase chain reaction
Progestin
siRNA
Stromal cells
Transfection
Wiskott-Aldrich syndrome
Wound healing
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Endometriosis, a common gynecological disorder characterized by the growth of endometrial gland and stroma outside the uterus, causes several symptoms such as dysmenorrhea, hypermenorrhea, and chronic abdominal pain. 17β estradiol (E2) stimulates the growth of endometriotic lesions. Although estetrol (E4), produced by human fetal liver, is also a natural estrogen, it may have the opposite effects on endometriotic cells. We investigated different effects of E4 and E2 on the invasion and migration of immortalized human endometrial stromal cells (HESCs) and evaluated whether E4 affects the expression of Wiskott-Aldrich syndrome protein (WASP) family member 1 (WASF-1). We measured the invasion of HESCs by a Matrigel chamber assay. Cell migration was measured by wound healing assay and cell tracking analysis. The expression of WASF-1 was confirmed by independent real-time PCR analysis. Transfection of cells with siRNAs was carried out to knock down the expression of WASF-1 in HESCs. E4 significantly inhibited E2-induced invasion and migration of HESCs. WASF-1 was found to be a potential mediator based on metastasis PCR array. WASF-1 was upregulated by E2 and downregulated by E4. Knockdown of WASF-1 inhibited migration. Our results suggest that E4 may inhibit E2-induced growth of endometriotic lesions. Downregulation of WASF-1 is involved in the inhibitory effects of E4 on migration. The use of E4 combined with progestins as combined oral contraceptives may cause endometriotic lesions to regress in women with endometriosis.
ISSN:0918-8959
1348-4540
DOI:10.1507/endocrj.EJ23-0397