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

Akihiko Wakatsuki, Yinzhi Lin, Shiori Kojima, Hiroshi Matsushita, Kosei Takeuchi, Kazuo Umezawa
Endocrine journal · 2024 · vol. 71(2) , pp. 199–206 · doi:10.1507/endocrj.EJ23-0397 · PMID:38171884
other OA: gold CC-BY-NC-ND-4.0
🔓 Open OA copy Full text JSON View on PubMed View at publisher
⚙ AI-generated summary by claude@2026-06, 2026-06-09 ⓘ

Estetrol (E4) inhibited estradiol (E2)-induced invasion and migration of human endometrial stromal cells by downregulating WASF-1 expression, suggesting E4's potential therapeutic role in endometriosis.

One-sentence paraphrase of the abstract; not a substitute for reading it. No clinical advice. How this works

⚙ AI-generated deep summary by claude@2026-06, 2026-06-10 · read from full text ⓘ

The paper investigated how the natural estrogen estetrol (E4), compared with 17β-estradiol (E2), affects invasion and migration of immortalized human endometrial stromal cells, and whether these effects involve Wiskott-Aldrich syndrome protein family member 1 (WASF-1). Using Matrigel invasion assays, wound-healing and cell-tracking migration analyses, and real-time PCR, the authors found that E4 significantly inhibited E2-induced invasion and migration, with WASF-1 upregulated by E2 and downregulated by E4; WASF-1 knockdown via siRNA reduced migration. A caveat is that the experiments were performed in immortalized cell lines rather than in patient-derived models or clinical samples. This paper is centrally about endometriosis — it tests whether E4 can counteract E2-driven invasive and migratory behavior in endometrial stromal cells via downregulation of WASF-1.

Read from the paper's body, not the abstract. Not a substitute for reading the paper. No clinical advice. How this works

Abstract

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.
Full text 1,974 characters · extracted from oa-doi-fallback · click to expand
NOTE Inhibitory effects of estetrol on the invasion and migration of immortalized human endometrial stromal cells 2024 Volume 71 Issue 2 Pages 199-206 Details Abstract 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. © The Japan Endocrine Society This article is licensed under a Creative Commons [Attribution-NonCommercial-NoDerivatives 4.0 International] license. https://creativecommons.org/licenses/by-nc-nd/4.0/deed.en Favorites & Alerts Recently viewed articles Predecessor

Text is read by the "Ask this paper" AI Q&A widget below. Extraction quality varies by source — PMC NXML preserves structure cleanly, OA-HTML may include some navigation residue, and OA-PDF can have broken hyphenation. The publisher copy (via DOI) is the canonical version.

My notes (saved in your browser only)

⚙ Ask this paper AI returns verbatim quotes from the full text · source: oa-doi-fallback ⓘ

Answers must be backed by verbatim quotes from this paper's full text. Hallucinated quotes are dropped automatically; if no verbatim passage answers the question, we say so. How this works

Condition tags

endometriosisdysmenorrhea

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Estetrol Estetrol Estetrol Estetrol Estetrol Estetrol Estetrol

Citation neighborhood (no data yet)

We don't have any in-corpus citations linked to this paper yet. This is a recent paper (2024) — citers typically take a year or two to land, and the OpenAlex reference graph may still be filling in.

Source provenance

europepmc
last seen: 2026-06-16T06:07:01.518242+00:00
pubmed
last seen: 2026-06-16T06:05:24.908163+00:00
unpaywall
last seen: 2026-05-14T19:30:52.867331+00:00
License: CC-BY-NC-ND-4.0 · commercial use OK · attribution required
Courtesy of the U.S. National Library of Medicine