ArticleThe Journal of clinical endocrinology and metabolism2011
Leiomyoma simultaneously impair endometrial BMP-2-mediated decidualization and anticoagulant expression through secretion of TGF-β3.
Article in The Journal of clinical endocrinology and metabolism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Endometrial Angiogenesis of Abnormal Uterine Bleeding and Infertility in Patients with Uterine Fibroids-A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Evaluating the Effect of Epigallocatechin Gallate (EGCG) in Reducing Folate Levels in Reproductive Aged Women by MTHFR and DHFR Genotype in Combination With Letrozole or Clomiphene.Clinical and translational science · 2025Trial
- Assessing the Hepatic Safety of Epigallocatechin Gallate (EGCG) in Reproductive-Aged Women.Nutrients · 2023Trial
- From prevalence to precision: Integrating phenotype, symptoms, reproductive goals, and treatment in leiomyoma care.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2026Review
- Mechanistic insights into inflammatory cytokines in adenomyosis‑induced infertility (Review).International journal of molecular medicine · 2026Review
- Cycle-Dependent Expression of Immune, Morphogenetic, Apoptotic, and Steroid-Related Markers in the Endometrium of Infertile Women: A Pilot Study.Current issues in molecular biology · 2026Article
- The epidemiology and pathogenesis of uterine fibroids.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2025Review
- Review
- A systems-based approach to uterine fibroids identifies differential splicing associated with abnormal uterine bleeding.Communications medicine · 2025Article
- Integral Roles of the TGFβ Signaling Pathway in Uterine Function and Disease.Endocrinology · 2025Review
- Mechanism of Endometrial Receptivity Affected by Fibroids.American journal of reproductive immunology (New York, N.Y. : 1989) · 2024Review
- Article
- Article
- Review
- The Role of TGF-β during Pregnancy and Pregnancy Complications.International journal of molecular sciences · 2023Review
- Infertility in patients with uterine fibroids: a debate about the hypothetical mechanisms.Human reproduction (Oxford, England) · 2023Article
- MED12 mutation activates the tryptophan/kynurenine/AHR pathway to promote growth of uterine leiomyomas.JCI insight · 2023Article
- Effects of Non-Cavity-Distorting Intramural Fibroids on IVF Outcomes in Patients with Recurrent IVF Failure: Does Myomectomy Change IVF Outcomes ?Journal of obstetrics and gynaecology of India · 2023Article
- Contemporary evaluation of women and girls with abnormal uterine bleeding: FIGO Systems 1 and 2.International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics · 2023Article
- The Diagnostics and Treatment of Recurrent Pregnancy Loss.Journal of clinical medicine · 2023Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
contextUterine leiomyomas occur in 30-70% of reproductive-age women. Leiomyoma reduce implantation, increase miscarriage risk, and increase menstrual bleeding. We hypothesized that endometrial defects induced by leiomyoma result in menorrhagia and reproductive dysfunction.
objectivesWe evaluated the effect of leiomyoma on endometrial gene expression essential for implantation and hemostasis both in vivo and in primary endometrial stromal cells (ESC). DESIGN AND
settingWe conducted a case control and in vitro study at a university medical center. PATIENTS: The study included 24 subjects with or without leiomyoma. INTERVENTION/MAIN OUTCOME MEASURED: Endometrium, myometrium, leiomyoma, and ESC were obtained. Immunohistochemistry was used to evaluate TGF-β3, bone morphogenetic protein (BMP) receptors (BMPRs), plasminogen activator inhibitor 1 (PAI-1), and thrombomodulin in vivo. BMP-2 secretion was assessed by ELISA. ESC were treated with recombinant human (rh) BMP-2 or rhTGF-β3. Expression of HOXA10, LIF, BMPRs, antithrombin III (ATIII), thrombomodulin, and PAI-1 was assessed by quantitative RT-PCR.
resultsESC from controls secreted more BMP-2 than those from women with leiomyoma. HOXA10 and LIF expression increased after rhBMP-2 treatment of normal but not leiomyoma-associated ESC. In vivo leiomyoma-associated endometrium expressed lower levels of BMPR 1A, 1B, and 2 than controls. Leiomyoma expressed high levels of TGF-β3; TGF-β3 treatment of ESC reduced expression of BMPRs. Similarly, leiomyoma-associated endometrium expressed less PAI-1 and thrombomodulin in vivo. In ESC, TGF-β3 reduced expression of PAI-1, ATIII, and thrombomodulin.
conclusionsLeiomyoma-secreted TGF-β3 induces BMP-2 resistance in endometrium by down-regulation of BMPR-2, likely causing defective endometrial decidualization. TGF-β3 also reduces expression of PAI-1, ATIII, and thrombomodulin in endometrium, likely contributing to menorrhagia. A single molecular signal targeting endometrium may mediate both leiomyoma-induced infertility and bleeding.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.