Increased expression of antimüllerian hormone and its receptor in endometriosis

To evaluate antimüllerian hormone (AMH) and AMH receptor II (AMHRII) mRNA and protein expression in endometrium and in ovarian or deep lesions of women with endometriosis

Urocortin 2 and urocortin 3 in endometriosis: evidence for a possible role in inflammatory response

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Altered expression of activin, cripto, and follistatin in the endometrium of women with endometrioma.

Objective: To evaluate the expression pattern of activin A, activin receptors, and activin modulators messenger RNA (mRNA) in the eutopic endometrium of patients with endometriosis at different phases of the menstrual cycle and to evaluate the mRNA expression of the same proteins in endometriomas during the menstrual cycle. Design: Prospective study. Setting: University hospital. Patient(s): Women with and without endometriosis. Intervention(s): Samples of endometrial and endometriotic tissue from women with endometrioma (n = 48), and endometrial samples from women without endometriosis (controls) (n = 48). Main Outcome Measure(s): Quantification of activin A, activin B, activin receptor II, nodal, cripto, inhibin α, and follistatin expression by real-time reverse-transcriptase polymerase chain reaction (RT-PCR). Result(s): The eutopic endometrium of patients with endometriosis showed [1] higher activin A mRNA expression in the proliferative phase and a lack of late secretory phase peak, [2] a lack of endometrial cycle-related variations of cripto and inhibin α mRNA expression, and [3] an inverse expression pattern of follistatin mRNA. Endometriomas showed similar variations in the expression of activin-related protein mRNA during the menstrual cycle as eutopic endometrium. Conclusion(s): The disturbed expression of endometrial activin A, cripto (activin receptor antagonist), and follistatin (activin-binding protein) suggests a dysfunction of the activin pathway in endometriosis. Endometriomas showed similar changes of activin-related proteins during the menstrual cycle, which supports a common biology for eutopic and ectopic endometrium in endometriosis. © 2011 by American Society for Reproductive Medicine

Heat-killed Lactobacillus rhamnosus GG modulates urocortin and citokine release in primary trophoblast cells

A number of studies are showing that probiotic treatment induces an anti-inflammatory state. Intrauterine infection can lead to preterm delivery by modulating immune function and efforts to prevent this condition are ongoing nowadays. Lactobacillus rhamnosus GG (LGG) is a probiotic known to ameliorate inflammation by increasing local anti-inflammatory mediators in urinary and gastrointestinal tracts. The present study then analyzed the effect of heat-killed LGG over β-hCG, progesterone, interleukins (IL) 4 and 10, tumor necrosis factor-α (TNF-α), corticotropin releasing hormone (CRH) and urocortin (Ucn) release by primary trophoblast cells. Normal human term placentas (n = 6) were collected and purified trophoblast cells were incubated in the presence of LGG, lipopolysaccharide (LPS) or either LGG + LPS during 3 h, after which the target substances were quantified by ELISA and real-time PCR. LGG did not affect β-hCG, progesterone, or CRH secretion. Conversely, LGG increased IL-4 protein and mRNA expression (P < 0.05) while IL-10 and Ucn secretion were increased in a dose dependent manner and the highest dose of LGG increased significantly IL-10 mRNA (P < 0.05). LGG did not alter TNF-α, while LPS exposure increased TNF-α protein (P < 0.001) and mRNA expression (P < 0.01). Conversely, LGG treatment reversed LPS-induced TNF-α release at both protein (P < 0.01) and mRNA levels (P < 0.05) in a dose dependent fashion. In conclusion, LGG stimulates IL-4, IL-10 and Ucn expression and reverses LPS-induced TNF-α release from trophoblast cells, with no change in β-hCG or progesterone release, suggesting that this probiotic may play a role as an immunomodulatory agent in human placenta without altering basic trophoblast functions. © 2010 Elsevier Ltd. All rights reserved

Activin a Stimulates Interleukin 8 and Vascular Endothelial Growth Factor Release From Cultured Human Endometrial Stromal Cells: Possible Implications for the Pathogenesis of Endometriosis.

Background: Activin A is an endometrial secretory product involved in inflammation and angiogenesis. The present study aimed to valuate the effect of activin A and its antagonist follistatin on interleukin (IL)-6, IL-8, and vascular endothelial growth factor (VEGF) expression and release from cultured human endometrial stromal cells (HESCs) from women with and without endometriosis. Methods: The HESCs were collected from women with endometriosis (n = 6) and controls (n = 6). Primary cultures were treated with activin A at different doses or activin A plus follistatin. The IL-6, IL-8, and VEGF messenger RNA expression was evaluated by real-time polymerase chain reaction and protein release was evaluated by enzyme-linked immunosorbent assay. Results: Unstimulated HESC from women with endometriosis secreted more IL-6 and IL-8 than controls. The addition of activin A increased IL-8 and VEGF secretion in HESC from controls and decreased IL-6 and IL-8 secretion in HESC from women with endometriosis. These effects were counteracted by follistatin. Conclusion: Activin A regulates the expression and secretion of IL-8 and VEGF in cultured HESC, and this mechanism appears to be disrupted in eutopic endometrial cells from women affected by endometriosis. activin; cell culture; cytokines; endometriosis; endometrium; follistatin; VEG

Urocortin and corticotrophin-releasing hormone receptor type 2 mRNA are highly expressed in deep infiltrating endometriotic lesions

Ovarian endometrioma (OMA) and deep infiltrating endometriosis (DIE) are the most severe forms of endometriosis, but different pathogenetic mechanisms and clinical symptoms distinguish these two forms. Corticotrophin-releasing hormone (CRH) and urocortin (Ucn) are endometrial neuropeptides involved in tissue differentiation and inflammation. The expression of CRH, Ucn, Ucn2, CRH-receptors (type-1 and type-2) and inflammatory enzymes phospholipase-A2 group IIA (PLA2G2A) and cycloxygenase-2 (COX2) were evaluated in OMA (n = 22) and DIE (n = 26). The effect of CRH or Ucn on COX2 mRNA expression was evaluated in cultured human endometrial stromal cells. In DIE lesions, CRH, Ucn and CRH-R2 mRNA levels were significantly higher than in OMA (P < 0.01, P < 0.001 and P < 0.05, respectively); DIE lesions showed a higher expression of COX2 (P < 0.01) and PLA2G2A (P < 0.05) mRNA than OMA, which was positively correlated with CRH-R2 mRNA expression (P < 0.05). Intense immunostaining for CRH and Ucn was shown in DIE. Treatment of cultured endometrial stromal cells with Ucn significantly increased COX2 mRNA expression (P < 0.01); this effect was reversed by the CRH-R2 antagonist astressin-2B. In DIE, DIE lesions highly express neuropeptide and enzyme mRNAs, supporting a strong activation of inflammatory pathways

FOXL2 in human endometrium:hyperexpressed in endometriosis

The present study investigated expression and protein localization of FOXL2 messenger RNA (mRNA) in endometrium of healthy women and in patients with endometriosis during endometrial cycle. In endometriotic lesions, FOXL2 mRNA and protein were evaluated and a possible correlation with activin A mRNA expression changes was also studied. Endometrium was collected from healthy women (n = 52) and from women with endometriosis (n = 31) by hysteroscopy; endometriotic tissues were collected by laparoscopy (n = 38). FOXL2 gene expression analysis in endometrium of healthy women showed a significant expression and no significant changes in mRNA levels between proliferative and secretory phases; a similar pattern was observed in endometrium of patients with endometriosis. Immunohistochemical evaluation showed that FOXL2 protein localized in stromal and glandular cells and colocalized with SUMO-1. FOXL2 mRNA expression was 3-fold higher in endometriosis than in healthy endometrium (P <.01) and a positive correlation between FOXL2 and activin A mRNA was found (P <.05) in endometriosis. In conclusion, FOXL2 mRNA expression and its protein localization do not change during endometrial cycle in eutopic endometrium from healthy individuals or patients with endometriosis; the hyperexpression of FOXL2 in endometriotic lesions suggests an involvement of this transcriptional regulator, probably associated with activin A expression and related to the pathogenesis of endometriosis. © The Author(s) 2014