Estrogen Receptors and Endometriosis

Chantalat, Élodie; Valera, Marie-Cécile; Vaysse, Charlotte; Noirrit, Emmanuelle; Rusidzé, Mariam; Weyl, Ariane; Vergriete, Kélig; Buscail, Étienne; Lluel, Philippe; Fontaine, Coralie; Arnal, Jean‐François; Lenfant, Françoise

doi:10.3390/ijms21082815

Cited by 156 publications

(133 citation statements)

References 89 publications

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“…Estrogen is heavily involved in many aspects of endometriosis, and the disease is also considered a hormone-dependent disease, as it bears symptoms restricted to the reproductive period and is responsive to hormonal treatment [ 47 , 51 ]. In fact, a 2017 study found that estrogen is necessary to induce endometriosis [ 52 ].…”

Section: Endometriosismentioning

confidence: 99%

Intricate Connections between the Microbiota and Endometriosis

Jiang

Yong

Allaire

et al. 2021

IJMS

103

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Imbalances in gut and reproductive tract microbiota composition, known as dysbiosis, disrupt normal immune function, leading to the elevation of proinflammatory cytokines, compromised immunosurveillance and altered immune cell profiles, all of which may contribute to the pathogenesis of endometriosis. Over time, this immune dysregulation can progress into a chronic state of inflammation, creating an environment conducive to increased adhesion and angiogenesis, which may drive the vicious cycle of endometriosis onset and progression. Recent studies have demonstrated both the ability of endometriosis to induce microbiota changes, and the ability of antibiotics to treat endometriosis. Endometriotic microbiotas have been consistently associated with diminished Lactobacillus dominance, as well as the elevated abundance of bacterial vaginosis-related bacteria and other opportunistic pathogens. Possible explanations for the implications of dysbiosis in endometriosis include the Bacterial Contamination Theory and immune activation, cytokine-impaired gut function, altered estrogen metabolism and signaling, and aberrant progenitor and stem-cell homeostasis. Although preliminary, antibiotic and probiotic treatments have demonstrated efficacy in treating endometriosis, and female reproductive tract (FRT) microbiota sampling has successfully predicted disease risk and stage. Future research should aim to characterize the “core” upper FRT microbiota and elucidate mechanisms behind the relationship between the microbiota and endometriosis.

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Section: Endometriosismentioning

confidence: 99%

Intricate Connections between the Microbiota and Endometriosis

Jiang

Yong

Allaire

et al. 2021

IJMS

103

View full text Add to dashboard Cite

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“…Studies have also shown that endometriotic cells can metabolize estradiol, potentially exacerbating the disease [ 51 , 52 ]. This de novo estrogen synthesis may be caused by available cholesterol coupled with increased aromatase [cytochrome p450, family 19a1 ( CYP19A1 )] and hydroxysteroid 17-beta dehydrogenase 1 ( HSD17β1 ) expression, critical enzymes involved in estradiol synthesis [ 53 , 54 , 55 ]. Large 12Z spheroids showed an 8.1-fold increase in CYP19A1 and a 23-fold increase in HSD17β1 in spheroid than monolayer cultures ( Figure 5 ).…”

Section: Resultsmentioning

confidence: 99%

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

et al. 2020

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Endometriosis occurs when endometrial-like tissue grows outside the uterine cavity, leading to pelvic pain, infertility, and increased risk of ovarian cancer. The present study describes the optimization and characterization of cellular spheroids as building blocks for Kenzan scaffold-free method biofabrication and proof-of-concept models of endometriosis and the endometriotic microenvironment. The spheroid building blocks must be of a specific diameter (~500 μm), compact, round, and smooth to withstand Kenzan biofabrication. Under optimized spheroid conditions for biofabrication, the endometriotic epithelial-like cell line, 12Z, expressed high levels of estrogen-related genes and secreted high amounts of endometriotic inflammatory factors that were independent of TNFα stimulation. Heterotypic spheroids, composed of 12Z and T-HESC, an immortalized endometrial stromal cell line, self-assembled into a biologically relevant pattern, consisting of epithelial cells on the outside of the spheroids and stromal cells in the core. 12Z spheroids were biofabricated into large three-dimensional constructs alone, with HEYA8 spheroids, or as heterotypic spheroids with T-HESC. These three-dimensional biofabricated constructs containing multiple monotypic or heterotypic spheroids represent the first scaffold-free biofabricated in vitro models of endometriosis and the endometriotic microenvironment. These efficient and innovative models will allow us to study the complex interactions of multiple cell types within a biologically relevant microenvironment.

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“…These are ovaries, which primarily convert cholesterol to estradiol and secrete it periodically into the circulation, peripheral tissues such as the adipose tissue and skin, that convert androstenedione to estrone in relatively small quantities, and endometriotic tissue, synthesizing de novo high amounts of estradiol from cholesterol via aromatase and steroidogenic acute regulatory protein (StAR) [ 73 ]. Contrary to endometriotic lesions, normal endometrium cannot synthesize estrogen due to these enzymes’ absence [ 75 ]. In endometriosis, local estradiol levels increase due to upregulation of estradiol-producing aromatase expression and reduction in 17β-HSD type 2 activity, implicated in the inactivation of estradiol through the oxidation to less active estrone [ 76 ].…”

Section: Molecular Targets In Endometriosis Dietary Managementmentioning

confidence: 99%

Polyphenols as a Diet Therapy Concept for Endometriosis—Current Opinion and Future Perspectives

2021

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Endometriosis represents an often painful, estrogen-dependent gynecological disorder, defined by the existence of endometrial glands and stroma exterior to the uterine cavity. The disease provides a wide range of symptoms and affects women’s quality of life and reproductive functions. Despite research efforts and extensive investigations, this disease’s pathogenesis and molecular basis remain unclear. Conventional endometriosis treatment implies surgical resection, hormonal therapies, and treatment with nonsteroidal anti-inflammatory drugs, but their efficacy is currently limited due to many side effects. Therefore, exploring complementary and alternative therapy strategies, minimizing the current treatments’ adverse effects, is needed. Plants are sources of bioactive compounds that demonstrate broad-spectrum health-promoting effects and interact with molecular targets associated with endometriosis, such as cell proliferation, apoptosis, invasiveness, inflammation, oxidative stress, and angiogenesis. Anti-endometriotic properties are exhibited mainly by polyphenols, which can exert a potent phytoestrogen effect, modulating estrogen activity. The available evidence derived from preclinical research and several clinical studies indicates that natural biologically active compounds represent promising candidates for developing novel strategies in endometriosis management. The purpose of this review is to provide a comprehensive overview of polyphenols and their properties valuable for natural treatment strategy by interacting with different cellular and molecular targets involved in endometriosis progression.

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Estrogen Receptors and Endometriosis

Cited by 156 publications

References 89 publications

Intricate Connections between the Microbiota and Endometriosis

Intricate Connections between the Microbiota and Endometriosis

Three-Dimensional Biofabrication Models of Endometriosis and the Endometriotic Microenvironment

Polyphenols as a Diet Therapy Concept for Endometriosis—Current Opinion and Future Perspectives

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