Identification of m6A Modification Regulated by Dysregulated circRNAs in Decidua of Recurrent Pregnancy Loss.

N6-methyladenosine (m6A) modification is a prevalent modification of messenger ribonucleic acid (mRNA) in eukaryote cells and is closely associated with recurrent pregnancy loss (RPL). Circular RNAs (circRNAs) play critical roles in embryo implantation, trophoblast invasion and immune balance, which are important events during pregnancy. However, how m6A modification is regulated by circRNAs and the potential regulatory mechanism of circRNAs on RPL occurrence remain largely unclassified.

Downregulation of CRHBP is associated with trophoblast invasion inhibition in recurrent pregnancy loss.

In Brief: Corticotropin-releasing hormone binding protein (CRHBP) is fundamental to the stress response and plays an important role in parturition during pregnancy. This study shows that abnormal CRHBP expression could be an early warning sign of recurrent pregnancy loss and that CRHBP knockdown could suppress HTR8/SVneo cell invasion by the PKC signaling pathway via interacting with CRH receptor 2.

Abstract: Trophoblast invasion is critical for placentation and pregnancy success.

Energy metabolism and maternal-fetal tolerance working in decidualization.

One pivotal aspect of early pregnancy is decidualization. The decidualization process includes two components: the differentiation of endometrial stromal cells to decidual stromal cells (DSCs), as well as the recruitment and education of decidual immune cells (DICs). At the maternal-fetal interface, stromal cells undergo morphological and phenotypic changes and interact with trophoblasts and DICs to provide an appropriate decidual bed and tolerogenic immune environment to maintain the survival of the semi-allogeneic fetus without causing immunological rejection.

Decidual Stromal Cell Ferroptosis Associated with Abnormal Iron Metabolism Is Implicated in the Pathogenesis of Recurrent Pregnancy Loss.

Iron is necessary for various critical biological processes, but iron overload is also dangerous since labile iron is redox-active and toxic. We found that low serum iron and decidual local iron deposition existed simultaneously in recurrent pregnancy loss (RPL) patients. Mice fed with a low-iron diet (LID) also showed iron deposition in the decidua and adverse pregnancy outcomes.

Tim-3 Coordinates Macrophage-Trophoblast Crosstalk via Angiogenic Growth Factors to Promote Pregnancy Maintenance.

T-cell immunoglobulin mucin-3 (Tim-3) is an important checkpoint that induces maternal-fetal tolerance in pregnancy. Macrophages (Mφs) play essential roles in maintaining maternal-fetal tolerance, remodeling spiral arteries, and regulating trophoblast biological behaviors. In the present study, the formation of the labyrinth zone showed striking defects in pregnant mice treated with Tim-3 neutralizing antibodies.

Tim-3/CTLA-4 pathways regulate decidual immune cells-extravillous trophoblasts interaction by IL-4 and IL-10.

To obtain a successful pregnancy, the establishment of maternal-fetal tolerance and successful placentation are required to be established. Disruption of this immune balance and/or inadequate placental perfusion is believed to be associated with a lot of pregnancy-related complications, such as recurrent spontaneous abortion, pre-eclampsia, and fetal intrauterine growth restriction. Extravillous trophoblasts (EVTs) have the unique ability to instruct decidual immune cells (DICs) to develop a regulatory phenotype for fetal tolerance.

Decreased level of Eomes+dCD8+ T cells with altered function might be associated with miscarriage.

The T-box transcription factor protein eomesodermin (Eomes) is known for both homeostasis and function of effector and memory CD8+T cells. However, much less is known about the functional regulation of Eomes on CD8+ T cells during pregnancy. In the present study, we concluded the higher Eomes expression dCD8+T cells during normal early pregnancy.

Eomesodermin regulate decidual CD4T cell function during human early pregnancy.

Decidual CD4T (dCD4T) cells play pivotal roles in inducing and maintaining maternal-fetal tolerance. Dysfunctional dCD4T cells are associated with miscarriage. In the present study, we demonstrated that the T-box transcription factor protein eomesodermin (Eomes) was involved in the functional regulation of dCD4T cells during early pregnancy.

Th17/Treg-cell balance in the peripheral blood of pregnant females with a history of recurrent spontaneous abortion receiving progesterone or cyclosporine A.

A successful pregnancy requires the maternal immune system to accept a fetus expressing allogeneic paternal antigens and provide competent responses to infections. Accordingly, maternal-fetal immune abnormalities may have an important role in the development of recurrent spontaneous abortion (RSA). Ever since the establishment of the association between immunologic abnormalities and RSA, various types of immune therapy to restore normal immune homeostasis have been increasingly developed.

Galectin-9 regulates HTR8/SVneo function via JNK signaling.

To obtain a successful pregnancy, trophoblasts must provide a physical barrier, suppress maternal reactivity, produce immunosuppressive hormones locally, and enhance the production of blocking factors that are able to bind to several antigenic sites. Inadequate placental perfusion has been closely associated with several pregnancy-associated diseases. Galectin-9 (Gal-9) has a wide variety of regulatory functions in innate and adaptive immunity during infection, tumor growth, and organ transplantation.

Dihydrotanshinone I Alleviates Spinal Cord Injury via Suppressing Inflammatory Response, Oxidative Stress and Apoptosis in Rats.

BACKGROUND Spinal cord injury (SCI) is a serious nervous system injury, causing extremely low quality of life and immensurable economic losses. However, there is few therapies that can effectively cure the injury. The goal of the present study was to explore the potential therapeutic effects of dihydrotanshinone I (DI) for SCI and the involving mechanism.

Altered frequency and function of spleen CTLA-4+Tim-3+ T cells are associated with miscarriage†.

Normal pregnancy is associated with several immune adaptations in both systemic and local maternal-fetal interface to allow the growth of semi-allogeneic conceptus. A failure in maternal immune tolerance to the fetus may result in abnormal pregnancies, such as recurrent spontaneous abortion. The regulation of T-cell homeostasis during pregnancy has important implications for maternal tolerance and immunity.

The appropriate frequency and function of decidual Tim-3CTLA-4CD8 T cells are important in maintaining normal pregnancy.

Maternal decidual CD8 T (dCD8 T) cells must integrate the antithetical demands of maternal-fetal tolerance and anti-viral immunity to establish a successful pregnancy. T-cell immunoglobulin mucin-3 (Tim-3) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) are two important co-inhibitory molecules that regulating CD8 T cells responses during infection and tumor. In the present study, we examined the co-expression of Tim-3 and CTLA-4 on CD8 T cells during pregnancy and found the higher frequency of Tim-3CTLA-4dCD8 T cells in response to trophoblasts.

Bidirectional regulation between 1st trimester HTR8/SVneo trophoblast cells and in vitro differentiated Th17/Treg cells suggest a fetal-maternal regulatory loop in human pregnancy.

Problem: During normal pregnancy, delicate crosstalk is established between fetus-derived trophoblasts and maternal immune cells to ensure maternal-fetal tolerance and successful placentation. Dysfunction in these interactions has been highly linked to certain pregnancy complications.

Method Of Study: Naïve CD4 T cells were cultivated with or without 1st trimester derived trophoblast cell line HTR8/SVneo cells in the absence or presence of T helper 17 (Th17) or regulatory (Treg)cell-inducing differentiation conditions.

Blockade of CTLA-4 and Tim-3 pathways induces fetal loss with altered cytokine profiles by decidual CD4T cells.

The single and/or combination use of immune checkpoint blockade therapies in human infectious diseases and cancer are rapidly expanding. Despite early efforts, substantial uncertainty remains about the safety and efficacy of immune checkpoint blockade in some populations. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and T-cell immunoglobulin mucin-3 (Tim-3) are the major targetable co-inhibitory receptors on T cells.

Distinct pattern of Th17/Treg cells in pregnant women with a history of unexplained recurrent spontaneous abortion.

The aim of the current study was to determine the pattern of immune cells and related functional molecules in peripheral blood and at the maternal-fetal interface in women with unexplained recurrent spontaneous abortion (URSA). In part I, 155 women were included and divided into four groups: non-pregnant controls with no history of URSA (NPCs), pregnant controls with no history of URSA (PCs), non-pregnant women with a history of URSA (NPUs), and pregnant women with a history of URSA (PUs). Venous blood samples were collected and analyzed.

[Efficacy and safety of mifepristone combined with misoprostol for termination of pregnancy between 8 and 16 weeks of gestation].

Objective: To assess the efficacy and safety of mifepristone combined with oral or vaginal misoprostol for termination of pregnancy between 8 and 16 weeks of gestation.

Methods: This was a randomized, multi-center, open clinical trial. A total of 625 women at 8-16 weeks of gestation were randomized to receive 200 mg oral mifepristone followed by either oral misoprostol 400 µg every 3 hours or vaginal misoprostol 400 µg every 6 hours for a maximum of 4 doses 36-48 hours later.

Opposing role of JNK-p38 kinase and ERK1/2 in hydrogen peroxide-induced oxidative damage of human trophoblast-like JEG-3 cells.

Trophoblasts play a crucial role in embryo implantation and maintenance of normal pregnancy. Recently, oxidative stress has been considered as one important factor in the pathogenesis of spontaneous abortion and preeclampsia. Many studies have reported that the plasma levels of hydrogen peroxide (H2O2) are significantly increased in women with preeclampsia, but the mechanisms involved in H2O2-induced cell cytotoxicity in trophoblasts are still not completely explained.

[Clinical efficacy and safety of megestrol acetate vaginal ring].

Objective: To explore the efficacy and safety of megestrol acetate silicone vaginal ring.

Methods: A total of 165 healthy child-bearing age women were recruited to examine the efficacy, safety and satisfaction rate of megestrol acetate silicone vaginal ring.

Results: The cumulative pregnancy rate of megestrol acetate silicone vaginal ring was 3.

Quantitative assessment of the influence of PPARG P12A polymorphism on gestational diabetes mellitus risk.

The peroxisome proliferator-activated receptor-γ (PPARG) is a member of the nuclear hormone receptor superfamily that has attracted considerable attention as a candidate gene for gestational diabetes mellitus (GDM) based on its function as a key factor involved in the regulation of adipocyte differentiation as well as lipid and glucose metabolism and insulin sensitivity. Many studies have examined the association between P12A polymorphism (rs1801282) in the PPARG gene and risk of GDM, but the results have been inconsistent. To derive a more precise estimation of the relationship, a meta-analysis of 2,858 GDM patients and 6,890 controls from nine published case-control studies was performed.