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...
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The Japan Endocrine Society
2024-02-01
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| Series: | Endocrine Journal |
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| Online Access: | https://www.jstage.jst.go.jp/article/endocrj/71/2/71_EJ23-0397/_html/-char/en |
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| author | Akihiko Wakatsuki Yinzhi Lin Shiori Kojima Hiroshi Matsushita Kosei Takeuchi Kazuo Umezawa |
| author_facet | Akihiko Wakatsuki Yinzhi Lin Shiori Kojima Hiroshi Matsushita Kosei Takeuchi Kazuo Umezawa |
| author_sort | Akihiko Wakatsuki |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-b42786ab84ae415095f66de8cc54d5f3 |
| institution | Kabale University |
| issn | 1348-4540 |
| language | English |
| publishDate | 2024-02-01 |
| publisher | The Japan Endocrine Society |
| record_format | Article |
| series | Endocrine Journal |
| spelling | doaj-art-b42786ab84ae415095f66de8cc54d5f32025-01-22T06:33:22ZengThe Japan Endocrine SocietyEndocrine Journal1348-45402024-02-0171219920610.1507/endocrj.EJ23-0397endocrjInhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cellsAkihiko Wakatsuki0Yinzhi Lin1Shiori Kojima2Hiroshi Matsushita3Kosei Takeuchi4Kazuo Umezawa5Department of Obstetrics and Gynecology, Aichi Medical University, Aichi 480-1195, JapanDepartment of Molecular Target Medicine, Aichi Medical University, Aichi 480-1195, JapanDepartment of Molecular Target Medicine, Aichi Medical University, Aichi 480-1195, JapanDepartment of Obstetrics and Gynecology, Aichi Medical University, Aichi 480-1195, JapanDepartment of Biology, Aichi Medical University, Aichi 480-1195, JapanDepartment of Molecular Target Medicine, Aichi Medical University, Aichi 480-1195, JapanEndometriosis, 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.https://www.jstage.jst.go.jp/article/endocrj/71/2/71_EJ23-0397/_html/-char/en17β estradiolestetrolendometriosisimmortalized human endometrial stromal cells |
| spellingShingle | Akihiko Wakatsuki Yinzhi Lin Shiori Kojima Hiroshi Matsushita Kosei Takeuchi Kazuo Umezawa Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells Endocrine Journal 17β estradiol estetrol endometriosis immortalized human endometrial stromal cells |
| title | Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells |
| title_full | Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells |
| title_fullStr | Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells |
| title_full_unstemmed | Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells |
| title_short | Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells |
| title_sort | inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells |
| topic | 17β estradiol estetrol endometriosis immortalized human endometrial stromal cells |
| url | https://www.jstage.jst.go.jp/article/endocrj/71/2/71_EJ23-0397/_html/-char/en |
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