Nomogram for predicting pathology upstaging in patients with EIN: is sentinel lymph node assessment useful in these patients?

Objective: The objective of this study was to identify the risk factors for postoperative pathological escalation of endometrial cancer in patients with a pathologic diagnosis of endometrial intraepithelial neoplasia (EIN) before surgery. Some of the clues from the preoperative assessment were used to build a nomogram to predict the likely pathological escalation after surgery, and to explore the feasibility of sentinel lymph node biopsy in these patients with possible pathological escalation.

Methods: This was a retrospective analysis of patients who underwent surgical treatment for EIN diagnosed before surgery between 2018 and 2023 in The Obstetrics and Gynecology Hospital of Fudan University.

An Estrogen-NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage.

Endometriosis is a common estrogen-dependent condition that impacts 8-10% of women in their reproductive age, resulting in notable pain, morbidity, and infertility. Despite extensive research endeavors, the precise cause of endometriosis remains elusive, and the mechanisms contributing to its associated infertility are still not well comprehended. Natural killer (NK) cells, vital innate immune cells crucial for successful pregnancy, have been investigated for their potential involvement in the pathogenesis of endometriosis.

Identification of potential biomarkers and immune infiltration characteristics in recurrent implantation failure using bioinformatics analysis.

Introduction: Recurrent implantation failure (RIF) is a frustrating challenge because the cause is unknown. The current study aims to identify differentially expressed genes (DEGs) in the endometrium on the basis of immune cell infiltration characteristics between RIF patients and healthy controls, as well as to investigate potential prognostic markers in RIF.

Methods: GSE103465, and GSE111974 datasets from the Gene Expression Omnibus database were obtained to screen DEGs between RIF and control groups.

An active glutamine/α-ketoglutarate/HIF-1α axis prevents pregnancy loss by triggering decidual IGF1GDF15NK cell differentiation.

Deficiency of decidual NK (dNK) cell number and function has been widely regarded as an important cause of spontaneous abortion. However, the metabolic mechanism underlying the crosstalk between dNK cells and embryonic trophoblasts during early pregnancy remains largely unknown. Here, we observed that enriched glutamine and activated glutaminolysis in dNK cells contribute to trophoblast invasion and embryo growth by insulin-like growth factor-1 (IGF-1) and growth differentiation factor-15 (GDF-15) secretion.

Hypoxia-hindered methylation of PTGIS in endometrial stromal cells accelerates endometriosis progression by inducing CD16 NK-cell differentiation.

Prostacyclin (PGI) plays key roles in shaping the immune microenvironment and modulating vasodilation, whereas its contribution to endometriosis (EMs) remains largely unclear. Our study suggested that prostacyclin synthase (PTGIS)-dependent PGI signaling was significantly activated in EMs, which was involved in the hypoxic microenvironment of ectopic lesions and deficient methylation status of the PTGIS promoter. Notably, in vitro assays, hypoxia promoted PTGIS expression through DNA methyltransferase 1 (DNMT1)-mediated DNA methylation deficiency in endometrial stromal cells (ESCs); PTGIS overexpression enhanced the adhesive ability of ESCs and led to elevated PGI production, and PGI triggered CD16 (encoded by FCGR3, Fc fragment of IgG receptor IIIa) natural killer (NK)-cell differentiation through PGI receptor (IP, PTGIR) in an ESC/NK-cell coculture system.

HIF1A-induced heme oxygenase 1 promotes the survival of decidual stromal cells against excess heme-mediated oxidative stress.

Heme oxygenase 1 (HO-1, encoded by the HMOX1 gene) is the rate-limiting enzyme that catalyzes heme degradation, and it has been reported to exert antioxidative effects. Recently, decidualization has been reported to confer resistance to environmental stress signals, protecting against oxidative stress. However, the effects and regulatory mechanism of HO-1 in decidual stromal cells (DSCs) during early pregnancy remain unknown.

Decidual IDO macrophage promotes the proliferation and restricts the apoptosis of trophoblasts.

Indoleamine 2, 3-dioxygenase (IDO), a tryptophan-catabolizing enzyme, is essential in physiological immunoregulation. The present research was conducted to elucidate the expression and roles of IDO in decidual macrophages (dMφ) during early pregnancy. Here, we observed a remarkable decrease of IDO dMφ from patients with unexplained recurrent spontaneous abortion (URSA).

Kynurenine promotes the cytotoxicity of NK cells through aryl hydrocarbon receptor in early pregnancy.

During early pregnancy, decidual NK (dNK) cells play indispensable roles in many processes including the decidualization, the implantation, and the maintenance of immune tolerance. Abnormal cytotoxic activity of NK cells can cause recurrent spontaneous abortion (RSA), while the regulatory mechanism of NK cytotoxicity remains to be unclear. In this study, we found that kynurenine in decidua and villus was in a comparable level between patients with RSA and normal pregnancy women.

The IFN-γ-IDO1-kynureine pathway-induced autophagy in cervical cancer cell promotes phagocytosis of macrophage.

Cervical cancer is a common malignant disease in female patients accompanied by activation of autophagy in tumor cells. However, the exact regulatory factors of autophagy and its effects on the immune response remain unknown. The induction of autophagy in HeLa and SiHa cells treated with IFN-γ, tryptophan depletion, kynurenine and epacadostat was detected by western blot analysis and by an autophagy detection kit.

Changes in subsets of immunocytes in endometrial hyperplasia.

Problem: Endometrial hyperplasia (EH) is characterized by an endometrial gland-to-stroma ratio >1 and is one of the most common gynecological diseases in the world. The role of immunocyte subsets in the development of EH remains unknown.

Methods: Patients who underwent dilatation and curettage due to abnormal uterine bleeding were recruited in the present study.

Collagen at the maternal-fetal interface in human pregnancy.

The survival and development of a semi-allogenic fetus during pregnancy require special immune tolerance microenvironment at the maternal fetal interface. During the establishment of a successful pregnancy, the endometrium undergoes a series of changes, and the extracellular matrix (ECM) breaks down and remodels. Collagen is one of the most abundant ECM.

Myeloid-derived suppressor cells in obstetrical and gynecological diseases.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of myeloid-origin cells which have immunosuppressive activities in several conditions, such as cancer and inflammation. Recent research has also associated MDSCs with numerous obstetrical and gynecological diseases. During pregnancy, MDSCs accumulate to ensure maternal-fetal immune tolerance, whereas they are decreased in patients who suffer from early miscarriage or pre-eclampsia.

Autophagy suppression of trophoblast cells induces pregnancy loss by activating decidual NK cytotoxicity and inhibiting trophoblast invasion.

Background: The crosstalk between trophoblast cells and decidual NK cells plays an important role in the establishment and maintenance of normal pregnancy. Recent studies reported that autophagy can induce immune tolerance at the maternal fetal interface, while the mechanism remains unclear.

Methods: Autophagy levels in the villi of normal and recurrent spontaneous abortion (RSA) patients were detected by transmission electron microscopy.

Decidual stromal cells maintain decidual macrophage homeostasis by secreting IL-24 in early pregnancy.

Problem: The state of self-renewal and self-maintain of decidual macrophages would be important for immune homeostasis at the maternal-fetal interface. The roles of interleukin (IL)-24 derived from decidual stromal cells (DSCs) on decidual macrophages have not been explored.

Method Of Study: IL-24 expression in DSCs was interfered by lentivirus, and the transcription levels of IL-24 in DSCs were verified by real time (RT)-PCR.

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies.

The survival and development of a semi-allogeneic fetus during pregnancy require the involvement of a series of cytokines and immune cells. Chemokines are a type of special cytokine those were originally described as having a role in leukocyte trafficking. CXC chemokine ligand (CXCL) 16 is a member of the chemokine family, and CXC chemokine receptor (CXCR) 6 is its sole receptor.

Role of Endometrial Autophagy in Physiological and Pathophysiological Processes.

Endometrium is the mucosal lining of the uterus which expressed a cyclic process of proliferation, secretion and scaling under the control of hormones secreted by the ovary, and it also plays an indispensable role in the embryo implantation, the constitution of fetal-maternal interface, and the maintaining of pregnancy. In pathophysiological conditions, the abnormality or disorder of endometrium may lead to endometrium-related diseases, such as endometriosis, endometrium hyperplasia and even endometrial carcinoma. In recent years, more and more evidence revealed that autophagy exists in both the endometrium stroma cells and epithelial cells, and the activity of autophagy is changed in the different phases of menstruation, as well as in the endometrium-related diseases.

Indoleamine 2,3-dioxygenase suppresses the cytotoxicity of 1 NK cells in response to ectopic endometrial stromal cells in endometriosis.

It has been reported that the impaired cytotoxicity of natural killer (NK) cells and abnormal cytokines that are changed by the interaction between ectopic endometrial cells and immune cells is indispensable for the initiation and development of endometriosis (EMS). However, the mechanism of NK cells dysfunction in EMS remains largely unclear. Here, we found that NK cells in peritoneal fluid from women with EMS highly expressed indoleamine 2,3-dioxygenase (IDO).

Bu-Shen-Yi-Qi formula impairs cytotoxicity of NK cells by up-regulating IDO expression in trophoblasts.

Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear.

Protopanaxadiol and metformin synergistically inhibit estrogen-mediated proliferation and anti-autophagy effects in endometrial cancer cells.

Metformin is commonly used for treating type II diabetes and has recently been reported to possess anti-proliferative properties that can be exploited for the prevention and treatment of a variety of cancers. Ginsenosides are the main effective biological components of ginseng. It has been reported that ginsenoside-Rb2 inhibit the invasiveness of endometrial cancer cells (ECC).