Rab27b promotes endometriosis by enhancing invasiveness of ESCs and promoting angiogenesis.

Problem: Endometriosis (EMS) is an estrogen-dependent disease which is characterized with estrogen-dependent growth of ectopic endometrium and increased local estrogen production. EMS performs tumor-like biological functions such as invasiveness and angiogenesis. Rab27b is a member of the Rab family of GTPases, which is strongly associated with the growth, invasion and metastasis of a variety of tumors.

Synergy between Th1 and Th2 responses during endometriosis: A review of current understanding.

Endometriosis is widely perceived as an estrogen-dependent chronic disorder with infertility and pelvic pain. Although the etiology of endometriosis has remained elusive, many studies have proclaimed the relevance of immune system disorders with endometriosis. With the discovery that the dysregulation of multiple biological functions in endometriosis is caused by the aberrant differentiation of T helper cells, a shift towards Th2 immune response may account for the disease progression.

Towards a Better Understanding of Endometriosis-Related Infertility: A Review on How Endometriosis Affects Endometrial Receptivity.

Endometriosis is the most common cause of infertility. Endometrial receptivity has been suggested to contribute to infertility and poor reproductive outcomes in affected women. Even though experimental and clinical data suggest that the endometrium differs in women with endometriosis, the pathogenesis of impaired endometrial receptivity remains incomplete.

ANP promotes HTR-8/SVneo cell invasion by upregulating protein kinase N 3 via autophagy inhibition.

Preeclampsia is a gestational disease characterized by two major pathological changes-shallow trophoblast invasion and impaired spiral artery remodeling. Atrial natriuretic peptide (ANP) is a kind of peptide hormone that regulates blood pressure, while the lack of active ANP participates in preeclampsia pathogenesis. However, the underlying mechanism of how ANP modulates trophoblasts function remains unclarified.

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.

RhoB Promotes Endometrial Stromal Cells Decidualization Via Semaphorin3A/PlexinA4 Signaling in Early Pregnancy.

Endometrial decidualization refers to a series of morphological changes and functional remodeling of the uterine endometrium to accept the embryo under the effect of estrogen and progesterone secreted by ovaries after ovulation. During decidualization, endometrial stromal cells (ESCs) proliferate and differentiate into decidual stromal cells, undergoing cytoskeletal rearrangement-mediated morphological changes and expressing decidualization markers, such as insulin-like growth factor-binding protein-1 and prolactin. Ras homology (Rho) proteins, a family of small G proteins, are well known as regulators of cellular morphology and involved in multiple other cellular processes.

SCM-198 Prevents Endometriosis by Reversing Low Autophagy of Endometrial Stromal Cell Balancing ERα and PR Signals.

Background: Endometriosis (EMS), an endocrine-related inflammatory disease, is characterized by estrogen and progesterone imbalance in ectopic lesions. However, its pathogenic mechanism has not been fully elucidated. While SCM-198 is the synthetic form of leonurine and has multiple pharmacological activities such as antioxidation and anti-inflammation, it remains unknown whether it could inhibit the progress of EMS by regulating estrogen signaling and inflammation.

SCM-198 Alleviates Endometriosis by Suppressing Estrogen-ERα mediated Differentiation and Function of CD4CD25 Regulatory T Cells.

Endometriosis (EMS), a typical endocrine immune disorder, associates with dramatically increased estrogen production and disorganized immune response in ectopic focus. Peritoneal regulatory T cells (Tregs) expansion in women with EMS and their pathogenic role attributable to endometriotic immunotolerance has been reported. Whether local high estrogen promotes EMS by discipling Tregs needs to be further explored.

A defective lysophosphatidic acid-autophagy axis increases miscarriage risk by restricting decidual macrophage residence.

Massive infiltrated and enriched decidual macrophages (dMφ) have been widely regarded as important regulators of maternal-fetal immune tolerance and trophoblast invasion, contributing to normal pregnancy. However, the characteristics of metabolic profile and the underlying mechanism of dMφ residence remain largely unknown. Here, we observe that dMφ display an active glycerophospholipid metabolism.

The risk of intrauterine exposure to SARS-CoV-2 in female COVID-19 patients: A comprehensive review.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new type of coronavirus that has caused fatal infectious diseases and global spread. This novel coronavirus attacks target cells through the interaction of spike protein and angiotensin-converting enzyme II (ACE2), leading to different clinical symptoms. However, for a successful pregnancy, a well-established in-uterine environment includes a specific immune environment, and multi-interactions between specific cell types are prerequisites.

Decidual CXCR4 CD56 NK cells as a novel NK subset in maternal-foetal immune tolerance to alleviate early pregnancy failure.

Natural killer (NK) cells preferentially accumulate at maternal-foetal interface and are believed to play vital immune-modulatory roles during early pregnancy and related immunological dysfunction may result in pregnant failure such as recurrent miscarriage (RM). However, the mechanisms underlying the establishment of maternal-foetal immunotolerance are complex but clarifying the roles of decidual NK (dNK) cells offers the potential to design immunotherapeutic strategies to assist RM patients. In this report, we analysed RNA sequencing on peripheral NK (pNK) and decidual NK cells during early pregnancy; we identified an immunomodulatory dNK subset CXCR4 CD56 dNK and investigated its origin and phenotypic and functional characteristics.

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).

Immune status of decidual macrophages is dependent on the CCL2/CCR2/JAK2 pathway during early pregnancy.

Problem: Decidual macrophages (dM ) play an important role in the formation of maternal-fetal immune tolerance. However, factors that influence the immune status of dM and the related potential mechanisms have not been elucidated to date.

Method Of Study: The gene transcription in dM , decidual stromal cells (DSCs), extravillous trophoblasts (EVTs), and peripheral monocytes (pMo) from human samples were measured using real-time polymerase chain reaction (PCR).

Regulatory T cells induce polarization of pro-repair macrophages by secreting sFGL2 into the endometriotic milieu.

An increased number of highly active regulatory T cells (Tregs) and macrophages has been found in peritoneal fluid from women with endometriosis. Here, we show that the level of Tregs-derived soluble fibrinogen-like protein 2 (sFGL2) increases in the peritoneal fluid of women with endometriosis. Higher expression of FGL2 and its receptor CD32B is observed in eutopic endometrium and ectopic tissues.

Crosstalk Between Trophoblasts and Decidual Immune Cells: The Cornerstone of Maternal-Fetal Immunotolerance.

The success of pregnancy relies on the fine adjustment of the maternal immune system to tolerate the allogeneic fetus. Trophoblasts carrying paternal antigens are the only fetal-derived cells that come into direct contact with the maternal immune cells at the maternal-fetal interface. The crosstalk between trophoblasts and decidual immune cells (DICs) via cell-cell direct interaction and soluble factors such as chemokines and cytokines is a core event contributing to the unique immunotolerant microenvironment.

Ovarian hormones-autophagy-immunity axis in menstruation and endometriosis.

Menstruation occurs in few species and involves a cyclic process of proliferation, breakdown and regeneration under the control of ovarian hormones. Knowledge of normal endometrial physiology, as it pertains to the regulation of menstruation, is essential to understand disorders of menstruation. Accumulating evidence indicates that autophagy in the endometrium, under the regulation of ovarian hormones, can result in the infiltration of immune cells, which plays an indispensable role in the endometrium shedding, tissue repair and prevention of infections during menstruation.

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.

Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways.

Background: Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies.

Rapamycin prevents spontaneous abortion by triggering decidual stromal cell autophagy-mediated NK cell residence.

Deficiency in decidualization has been widely regarded as an important cause of spontaneous abortion. Generalized decidualization also includes massive infiltration and enrichment of NK cells. However, the underlying mechanism of decidual NK (dNK) cell residence remains largely unknown.

CXCL12 in normal and pathological pregnancies: A review.

The survival of allogeneic fetuses during pregnancy is a rather paradoxical phenomenon with a complex mechanism. Chemokine ligand12 (CXCL12) and its receptors CXC chemokine receptor (CXCR)4 and 7 are extensively found in placenta tissues and cells, including trophoblast cells, vascular endothelial cells, and decidual stromal and decidual immune cells (eg, NK cells and regulatory T cells). Evidence has illustrated that the CXClL12/CXCR4/CXCR7 axis could enhance the cross talk at the maternal-fetal interface through multiple processes, such as invasion and placental angiogenesis, which appears to be critical signaling components in placentation and fetal outcome.

[Research advances on adrenergic receptor signaling involved in disease microenvironment through regulation of macrophages].

Adrenergic receptor (AR), one of the key receptors for nervous system, plays an important role in the immune microenvironment and the progression of many diseases. In recent years, the regulation of ARs and its signal on macrophages has become a research hotspot. Researchers found that ARs could exert different regulatory functions on macrophages in different microenvironments, which in turn affects occurrence and development of diseases such as tumor, heart failure, obesity, acute injury, infection and pregnancy-related diseases.