Platelets are an unindicted culprit in the development of endometriosis: clinical and experimental evidence

Ding, Ding; Liu, Xishi; Duan, Jie; Guo, Sun‐Wei

doi:10.1093/humrep/dev025

Cited by 110 publications

(147 citation statements)

References 81 publications

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“…We found recently that platelets are significantly aggregated in ovarian cysts and that activated platelets induce epithelial-mesenchymal transition (EMT) and subsequent myofibroblast activation, resulting in the acquisition of the smooth muscle cell marker, increased contractility, and increased production of collagen I (D. Ding, MSc, unpublished data, January 2015). 16 As myofibroblasts are known to be the primary extracellular matrix (ECM) secreting cells during wound healing and fibrosis, 17 our data provide evidence that endometriosis are wounds that undergo repeated tissue injury (bleeding) and repair, ultimately leading to fibrosis.…”

Section: Introductionmentioning

confidence: 83%

Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications

et al. 2015

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This study was undertaken to test the hypotheses that, due to gradual accumulation of dead erythrocytes and their ingested products resulting from repeated hemorrhage, older endometriomas (whitish in color) contain chocolate fluid with higher iron content than younger (brownish/blackish in color) ones with concomitant higher collagen content and more adhesions. We recruited 30 premenopausal women with histologically confirmed ovarian endometriomas and collected samples of their endometriotic lesions and chocolate fluid and measured the viscosity, density, and the concentration of total bilirubin, ferritin, and free iron of the chocolate fluid. We also evaluated the lesion color and adhesion scores. In addition, we performed Masson trichrome and Picro-Sirius red staining on all endometriotic cysts and evaluated the extent of fibrosis in the lesions. We found that fluids taken from white-colored endometriomas had significantly higher concentration of total bilirubin, ferritin, and free iron, respectively, than black/brown-colored ones. In addition, older cysts had fluids that had significantly higher density and viscosity. Fluid density correlated positively with the concentrations of total bilirubin, ferritin, and free iron. Older lesions had significantly more collagen content and higher adhesion scores. Taken together, these data supports the notion that older cysts, having experienced more bleeding episodes, contain chocolate fluid that is higher in viscosity, density, and iron content and higher fibrotic content than younger ones. This provides another piece of evidence that endometriotic lesions are wounds that undergo repeated injury and repair, resulting ultimately fibrotic lesions that are resistant to hormonal treatment.

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Section: Introductionmentioning

confidence: 83%

Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications

et al. 2015

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“…Platelets aggregate in ovarian cysts and promote epithelial-mesenchymal transition, characterized by acquisition of specialized smooth muscle cell markers, such as desmin, oxytocin receptor, and smooth muscle myosin heavy chain. 28 Guo et al 46 found that fluid from endometriomas from older patients also contains significantly higher concentration of total bilirubin, ferritin, and free iron when compared to younger women. In addition, older lesions have significantly more collagen content, higher adhesion scores, and contain more viscous fluid.…”

Section: The Progressive Phenotype Of Ovarian Endometriomasmentioning

confidence: 99%

Origins and Progression of Adolescent Endometriosis

et al. 2016

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Accumulating evidence indicates that adolescent endometriosis is common and often severe. Here we explore the possibility that seeding of naive endometrial progenitor cells into the pelvic cavity early in life, that is, at the time of neonatal uterine bleeding or soon after the menarche, results in more florid and progressive disease, characterized by highly angiogenic implants, recurrent ectopic bleeding, and endometrioma formation. We discuss the potential intergenerational risk factors associated with earlyonset endometriosis and explore the molecular drivers of disease progression. Taken together, the available data suggest that an increased focus on early-life events may help to identify young women at risk of severe, progressive endometriosis.

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“…We have recently shown increased platelet aggregation in endometriotic lesions and there are crosstalks between endometriotic stromal cells and platelets [11]. In addition, treatment of endometriotic stromal cells with activated platelets results in the upregulation of COX-2, VEGF, MMP-9, and Bcl-2 [11].…”

Section: Introductionmentioning

confidence: 99%

Activated Platelets Induce Estrogen Receptor β Expression in Endometriotic Stromal Cells

Zhang

Ding²,

Liu³

et al. 2015

Gynecol Obstet Invest

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Background/Aims: Endometriosis is viewed first and foremost as an estrogen-dependent disease, featuring not only excessive estrogen production but also aberrant expression of estrogen receptors (ERs), particularly ERβ, that mediate the estrogen action. ERβ is the predominant ER in mediating estrogen action in endometriosis, and estrogen plays a vital role in the development of endometriosis; thus, ERβ is viewed as a strong candidate for therapeutic targeting. Given our recent finding that platelets aggregate in endometriotic lesions, we sought to investigate whether activated platelets can upregulate ERβ. Methods: Using primary endometriotic stromal cells derived from patients with ovarian endometriomas and platelets harvested from healthy donors, we performed real-time RT-PCR analysis of mRNA abundance (n = 8) and Western blot analysis of protein expression (n = 8) of ERα and ERβ when co-cultured with phosphate-buffered saline, platelets, thrombin alone, and platelets plus thrombin for 48 h. Results: Treatment of endometriotic stromal cells with activated platelets resulted in the upregulation of ERβ gene and protein expression. Conclusion: In the presence of aggregated and thus activated platelets in endometriotic lesions, ERβ, but not ERα, is upregulated in endometriotic stromal cells. Our result suggests that the use of antiplatelet therapy may have potential in the treatment of endometriosis.

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Platelets are an unindicted culprit in the development of endometriosis: clinical and experimental evidence

Cited by 110 publications

References 81 publications

Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications

Dating Endometriotic Ovarian Cysts Based on the Content of Cyst Fluid and its Potential Clinical Implications

Origins and Progression of Adolescent Endometriosis

Activated Platelets Induce Estrogen Receptor β Expression in Endometriotic Stromal Cells

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