Impaired secretion of C-X-C motif chemokine ligand 10 by stimulation with a Toll-like receptor 4 ligand in endometrial epithelium of infertile patients with minimal-to-mild endometriosis.

Successful embryo implantation requires transient, well-controlled inflammation in decidualizing cells. In mice, Toll-like receptor (TLR) 4 signaling in endometrial epithelial cells (EECs) by stimulation with factors present in seminal fluids has been shown to be a key upstream driver of a controlled inflammatory response. Clinical evidence supports that exposure of the female reproductive tract to seminal plasma promotes implantation success.

IL-10 is not anti-fibrotic but pro-fibrotic in endometriosis: IL-10 treatment of endometriotic stromal cells in vitro promotes myofibroblast proliferation and collagen type I protein expression.

Study Question: Is interleukin-10 (IL-10) anti-fibrotic in endometriosis?

Summary Answer: IL-10 is not anti-fibrotic but pro-fibrotic in endometriosis, because IL-10 treatment of endometriotic stromal cells in vitro promotes myofibroblast proliferation and collagen type I protein expression.

What Is Known Already: We previously showed that persistent activation of signal transducer and activator of transcription 3 (STAT3) via IL-6 trans-signaling promotes fibrosis of endometriosis. Studies showed marked anti-fibrotic effects of IL-10 via the STAT3 signaling pathway, which is generally considered to be anti-inflammatory, in various organs.

Persistent activation of signal transducer and activator of transcription 3 via interleukin-6 trans-signaling is involved in fibrosis of endometriosis.

Study Question: Is activation of signal transducer and activator of transcription 3 (STAT3) via interleukin-6 (IL-6) trans-signaling involved in fibrosis of endometriosis?

Summary Answer: Persistent activation of STAT3 via IL-6 trans-signaling is involved in fibrosis of endometriosis.

What Is Known Already: Our previous study showed that sustained low-grade inflammation promotes a fibrotic phenotype in endometriotic stromal cells. However, the underlying mechanisms of the establishment of non-resolving, low-grade inflammation in endometriosis remain to be clarified.

[Avenues of reflection for endometriosis research in France].

Endometriosis is a chronic disease in which lesions resembling endometrial tissue are found outside the uterus, mainly in the pelvis or abdomen. It may affect 10% of women of childbearing age. It is the cause of a significant alteration in quality of life and a major cost to the health system.

Mechanobiology of the female reproductive system.

Background: Mechanobiology in the field of human female reproduction has been extremely challenging technically and ethically.

Methods: The present review provides the current knowledge on mechanobiology of the female reproductive system. This review focuses on the early phases of reproduction from oocyte development to early embryonic development, with an emphasis on current progress.

Hyperactivation of dormant primordial follicles in ovarian endometrioma patients.

Serum anti-Müllerian hormone (AMH) levels decrease after surgical treatment of ovarian endometrioma. This is the main reason that surgery for ovarian endometrioma endometriosis is not recommended before in vitro fertilization, unless the patient has severe pain or suspected malignant cysts. Furthermore, it has been suggested that ovarian endometrioma itself damages ovarian reserve.

Effects of Low Intraperitoneal Pressure on Quality of Postoperative Recovery after Laparoscopic Surgery for Genital Prolapse in Elderly Patients Aged 75 Years or Older.

Study Objective: Previous clinical trials for laparoscopic surgery have included few elderly patients aged ≥75 years. We aimed to evaluate the quality of postoperative recovery after laparoscopic surgery using low intraperitoneal pressure (IPP) (6 mm Hg) and warmed, humidified carbon dioxide gas for genital prolapse in elderly patients aged ≥75 years.

Design: Prospective consecutive case series.

Dose-dependent pro- or anti-fibrotic responses of endometriotic stromal cells to interleukin-1β and tumor necrosis factor α.

Endometriosis are characterized by dense fibrous tissue. Numerous studies have investigated roles of inflammation on the pathophysiology of endometriosis. However, the interplay of inflammation and fibrosis remains to be clarified.

In vitro and in vivo effects of MK2206 and chloroquine combination therapy on endometriosis: autophagy may be required for regrowth of endometriosis.

Background And Purpose: A high recurrence rate after medical treatment is a major clinical problem for patients with endometriosis. Here, we have evaluated the in vitro effects of combined treatment with MK2206 (an AKT inhibitor) + chloroquine on cell growth and regrowth of endometriotic stromal cells and the in vivo effects on endometriotic implants in a mouse xenograft model of endometriosis.

Experimental Approach: We evaluated the effects of autophagy inhibition by knockdown of the ATG13, Beclin-1 and ATG12 genes and pharmacological agents (chloroquine, bafilomycin A1 or 3-methyalanine) individually and in combination with MK2206 on cell growth and/or cell regrowth of endometriotic stromal cells in vitro.

Effects of low intraperitoneal pressure and a warmed, humidified carbon dioxide gas in laparoscopic surgery: a randomized clinical trial.

Laparoscopic surgery technology continues to advance. However, much less attention has been focused on how alteration of the laparoscopic surgical environment might improve clinical outcomes. We conducted a randomized, 2 × 2 factorial trial to evaluate whether low intraperitoneal pressure (IPP) (8 mmHg) and/or warmed, humidified CO (WH) gas are better for minimizing the adverse impact of a CO pneumoperitoneum on the peritoneal environment during laparoscopic surgery and for improving clinical outcomes compared to the standard IPP (12 mmHg) and/or cool and dry CO (CD) gas.

Effects of matrix stiffness on epithelial to mesenchymal transition-like processes of endometrial epithelial cells: Implications for the pathogenesis of endometriosis.

Endometriosis is defined as the presence of endometrial glands and stroma within extrauterine sites. Our previous study revealed an epithelial to mesenchymal transition (EMT)-like process in red peritoneal endometriosis, whereas membrane localization of E-cadherin was well maintained in epithelial cells of deep infiltrating endometriosis (DIE). Here we show that endometrial epithelial cells (EEE) grown on polyacrylamide gel substrates (PGS) of 2 kilopascal (kPa), a soft matrix, initiate a partial EMT-like process with transforming growth factor-β1 (TGF-β1) stimulation.

Effects of U0126 and MK2206 on cell growth and re-growth of endometriotic stromal cells grown on substrates of varying stiffness.

Endometriosis is a common gynecological disorder responsible for infertility and pelvic pain. A complete cure for patients with endometriosis awaits new targets and strategies. Here we show that U0126 (a MEK inhibitor) and MK2206 (an AKT inhibitor) synergistically inhibit cell growth of deep endometriotic stromal cells (DES) grown on polyacrylamide gel substrates (PGS) of varying stiffness (2 or 30 kilopascal [kPa]) or plastic in vitro.

Soft matrices inhibit cell proliferation and inactivate the fibrotic phenotype of deep endometriotic stromal cells in vitro.

Study Question: Can deep infiltrating endometriotic stromal cells (DES) sense changes in extracellular matrix (ECM) stiffness and respond to them?

Summary Answer: Soft matrices inhibit cell proliferation and inactivate the fibrotic phenotype of DES in vitro.

What Is Known Already: Deep infiltrating endometriosis (DIE) is characterized histologically by dense fibrous tissue. Tissue stiffening is a hallmark of fibrosis.

Co-operation between the AKT and ERK signaling pathways may support growth of deep endometriosis in a fibrotic microenvironment in vitro.

Study Question: How can deep endometriotic stromal cells proliferate and persist in a fibrotic environment?

Summary Answer: The serine/threonine kinase AKT and extracellular regulated kinase (ERK) signaling pathways may co-operate to support growth of deep endometriotic lesions by enhancing endometriotic stromal cell proliferation and survival in a fibrotic microenvironment in vitro.

What Is Known Already: Endometriosis, particularly deep infiltrating endometriosis, is characterized histologically by dense fibrous tissue that is primarily composed of type I collagen. This tissue may cause pelvic pain and infertility, which are major clinical issues associated with endometriosis.

Antifibrotic properties of epigallocatechin-3-gallate in endometriosis.

Study Question: Is epigallocatechin-3-gallate (EGCG) treatment effective in the treatment of fibrosis in endometriosis?

Summary Answer: EGCG appears to have antifibrotic properties in endometriosis.

What Is Known Already: Histologically, endometriosis is characterized by dense fibrous tissue surrounding the endometrial glands and stroma. However, only a few studies to date have evaluated candidate new therapies for endometriosis-associated fibrosis.

Targeting the Wnt/β-catenin pathway in endometriosis: a potentially effective approach for treatment and prevention.

Endometriosis is a chronic, estrogen-dependent disease associated with infertility and pelvic pain. Endometriosis is defined by the presence of extra-uterine endometrial tissue. It affects approximately 10% of reproductive-aged women.

Involvement of the Wnt/β-catenin signaling pathway in the cellular and molecular mechanisms of fibrosis in endometriosis.

Background: During the development and progression of endometriotic lesions, excess fibrosis may lead to scarring, chronic pain, and altered tissue function. However, the cellular and molecular mechanisms of fibrosis in endometriosis remain to be clarified.

Objectives: The objective of the present study was to investigate whether the Wnt/β-catenin signaling pathway was involved in regulating the cellular and molecular mechanisms of fibrosis in endometriosis in vitro and to evaluate whether fibrosis could be prevented by targeting the Wnt/β-catenin pathway in a xenograft model of endometriosis in immunodeficient nude mice.

In vitro effects of a small-molecule antagonist of the Tcf/ß-catenin complex on endometrial and endometriotic cells of patients with endometriosis.

Background: Our previous studies suggested that aberrant activation of Wnt/ß-catenin signaling might be involved in the pathophysiology of endometriosis. We hypothesized that inhibition of Wnt/ß-catenin signaling might result in inhibition of cell proliferation, migration, and/or invasion of endometrial and endometriotic epithelial and stromal cells of patients with endometriosis.

Objectives: The aim of the present study was to evaluate the effects of a small-molecule antagonist of the Tcf/ß-catenin complex (PKF 115-584) on cell proliferation, migration, and invasion of endometrial and endometriotic epithelial and stromal cells.

Adenosine triphosphate-binding cassette transporter G2 expression in endometriosis and in endometrium from patients with and without endometriosis.

Objective: To investigate adenosine triphosphate (ATP)-binding cassette transporter G2 (ABCG2) expression in endometriosis and in samples of endometrium from patients with and without endometriosis.

Design: Prospective study.

Setting: University hospital.

Impact of intraperitoneal pressure of a CO2 pneumoperitoneum on the surgical peritoneal environment.

Background: Animal experiments have suggested that a high intraperitoneal pressure (IPP) might adversely affect the surgical peritoneal environment. The present experimental study investigates the impact of IPP of a CO(2) pneumoperitoneum on human peritoneum.

Methods: Patients undergoing laparoscopic surgery were subjected to either low (8 mmHg) or standard (12 mmHg) IPP.

Epithelial to mesenchymal transition-like and mesenchymal to epithelial transition-like processes might be involved in the pathogenesis of pelvic endometriosis.

Background: Endometrium is derived from intermediate mesoderm via mesenchymal to epithelial transition (MET) during development of the urogenital system. By retaining some imprint of their mesenchymal origin, endometrial epithelial cells may be particularly prone to return to this state, via epithelial to mesenchymal transition (EMT). We hypothesized that pelvic endometriosis originates from retrograde menstruation of endometrial tissue and that EMT-like and MET-like processes might be involved in the pathogenesis of pelvic endometriosis.