Epigenetic drug screening for trophoblast syncytialization reveals a novel role for MLL1 in regulating fetoplacental growth.

Background: Abnormal placental development is a significant factor contributing to perinatal morbidity and mortality, affecting approximately 5-7% of pregnant women. Trophoblast syncytialization plays a pivotal role in the establishment and maturation of the placenta, and its dysregulation is closely associated with several pregnancy-related disorders, including preeclampsia and intrauterine growth restriction. However, the underlying mechanisms and genetic determinants of syncytialization are largely unknown.

The role of extravillous trophoblasts and uterine NK cells in vascular remodeling during pregnancy.

Successful embryo implantation requires both a receptive endometrium and competent blastocysts. After implantation, the maternal decidua undergoes a series of changes, including uterine spiral artery (SA) remodeling to accommodate the fetus and provide nutrients and oxygen for the fetus to survive. Uterine spiral arteries transform from small-diameter, high-resistance arteries to large-diameter and low-resistance arteries during pregnancy.

Elevated histone demethylase KDM5C increases recurrent miscarriage risk by preventing trophoblast proliferation and invasion.

KDM5C is a histone H3K4-specific demethylase, which has been shown to play a key role in biological disease and development. However, the role of KDM5C in trophoblasts at early pregnancy is currently unknown. Here, we showed that KDM5C was upregulated in placental trophoblasts from recurrent miscarriage (RM) patients compared with healthy controls (HCs).

Peroxiredoxin2 regulates trophoblast proliferation and migration through SPIB-HDAC2 pathway.

Adequate proliferation and migration of placental trophoblasts is the prerequisite of a successful pregnancy. Peroxiredoxin2 (Prdx2) is a multi-functional gene involved in various signal events to maintain essential biological functions and normal cellular homeostasis. In this study, substantially lower Prdx2 levels were found in the first trimester cytotrophoblasts of women who suffered from recurrent miscarriage (RM).

Retraction Notice to: Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR.

[This retracts the article DOI: 10.1016/j.omtn.

TCF3 regulates human endometrial stromal cell proliferation and migration in RPL.

Recurrent pregnancy loss (RPL) is a multifactorial condition with no explanation of miscarriage in approximately half of the RPL patients, consequently leaving deep physical and emotional sequels. Transcription factor 3 (TCF3 or E2A), is a unique member of the LEF/TCF family and plays an important role in embryogenesis. However, its function in RPL is poorly understood.

CLDN1 regulates trophoblast apoptosis and proliferation in preeclampsia.

Preeclampsia is a gestational hypertensive disease; however, preeclampsia remains poorly understood. Bioinformatics analysis was applied to find novel genes involved in the pathogenesis of preeclampsia and identified CLDN1 as one of the most differentially expressed genes when comparing patients with preeclampsia and healthy controls. The results of the qRT-PCR, Western blotting and immunohistochemistry experiments demonstrated that CLDN1 was significantly downregulated in the chorionic villi in samples from patients with preeclampsia.

Proteomic analysis of decidua in patients with recurrent pregnancy loss (RPL) reveals mitochondrial oxidative stress dysfunction.

Background: Pregnancy is a complicated physiological process. The multifaceted regulation of maternal-fetal interface is of great importance for maintaining normal pregnancy and avoiding fetal rejection and secondary abortion. Previous studies have focused on the clinical features or pathological biomarkers of fetal rejection and abortion.

PDIA3 regulates trophoblast apoptosis and proliferation in preeclampsia via the MDM2/p53 pathway.

Protein disulfide isomerase 3 (PDIA3) is a chaperone protein that modulates the folding of newly synthesized glycoproteins, has isomerase and redox activity, and has been implicated in the pathogenesis of many diseases. However, the role of PDIA3 in pregnancy-associated diseases remains largely unknown. Our present study reveals a key role for PDIA3 in the biology of placental trophoblasts from women with preeclampsia (PE).

Upregulation of RND3 Affects Trophoblast Proliferation, Apoptosis, and Migration at the Maternal-Fetal Interface.

Trophoblasts as the particular cells of the placenta play an important role in implantation and formation of the maternal-fetal interface. RND3 (also known as RhoE) is a unique member of the Rnd subfamily of small GTP-binding proteins. However, its function in cytotrophoblasts (CTBs) at the maternal-fetal interface is poorly understood.

SPRY4 regulates trophoblast proliferation and apoptosis via regulating IFN-γ-induced STAT1 expression and activation in recurrent miscarriage.

Problem: The dysregulation of trophoblast functions is one of the leading causes of recurrent miscarriage (RM), which frustrates 1%-5% of couples of childbearing ages. Sprouty 4 (SPRY4) is considered as a tumour suppressor and exerts a negative role in cell viability. However, its role in regulating trophoblast behaviors at the maternal-fetal interface remains largely unknown.

PDL1 blockage increases fetal resorption and Tfr cells but does not affect Tfh/Tfr ratio and B-cell maturation during allogeneic pregnancy.

A successful pregnancy requires sophisticated regulation of uterine microenvironment to guarantee the existence of semi-allogeneic conceptus without immune rejection. T follicular regulatory (Tfr) cells exert a suppressive effect on Tfh-cell expansion, B-cell response, and antibody production. Although accumulating evidence has demonstrated that dysregulations of Tfr cells can bring on various immunological diseases, their immunomodulatory roles during pregnancy still remain unheeded.

Upregulation of PUM1 Expression in Preeclampsia Impairs Trophoblast Invasion by Negatively Regulating the Expression of the lncRNA HOTAIR.

Pumilio (PUM) proteins are members of a highly conserved RNA-binding protein family that posttranscriptionally regulate gene expression in many organisms. However, their roles in the placenta are unclear. In the present study, we report the requirement for the PUM homolog 1 (PUM1) gene in preeclampsia (PE).

Urothelial carcinoma associated 1 promotes trophoblast invasion by regulating MMP9.

Background: The long non-coding RNA UCA1 is reportedly increased in several human tumors and critical for the cell migration, invasion, or proliferation of several cancer cells. However, the potential roles of UCA1 in trophoblasts at early pregnancy still poorly understood. Here, we sought to unravel the roles of UCA1 in the occurrence of the recurrent miscarriage (RM) disorders.

ANXA7 regulates trophoblast proliferation and apoptosis in preeclampsia.

Problem: Preeclampsia (PE) is a unique gestational disorder leading to maternal and neonatal morbidity and mortality. AnnexinA7 (ANXA7) is a calcium-dependent phospholipid-binding protein that promotes membrane fusion during exocytosis. However, the function of ANXA7 in placental trophoblast is poorly understood.

The orphan nuclear receptor NUR77 promotes trophoblast invasion at early pregnancy through paracrine placental growth factor.

NR4A1 (NUR77) is an orphan nuclear receptor that has been implicated in both cell survival and apoptosis. However, the role of NUR77 in trophoblast function during early placenta development has not been fully elucidated. In this study, we showed that NUR77 expression was significantly lower in the villi of the recurrent miscarriage (RM) group compared to that in the healthy controls (HCs) group.

The m6A demethylase ALKBH5 controls trophoblast invasion at the maternal-fetal interface by regulating the stability of mRNA.

N-Methyladenosine (mA) is the most prevalent internal modification in mammalian mRNAs. Although mA is important in many biological processes, its roles in the placenta are unclear. : Levels of global mRNA mA methylation and ALKBH5 expression in recurrent miscarriage (RM) patients were determined using quantitative reverse transcription-PCR (qRT-PCR), mA RNA methylation quantification, and immunohistochemical methods.

Downregulation of CCNA2 disturbs trophoblast migration, proliferation, and apoptosis during the pathogenesis of recurrent miscarriage.

Problem: Recurrent miscarriage (RM) is defined as two or more pregnancy losses until 24 weeks of gestation, which distresses up to 1-5% of couples worldwide. Cyclin A2 (CCNA2) regulates the cell cycle by promoting transition through G1/S and G2/M. Little is known about CCNA2's functions in trophoblast, although it is highly expressed in the placenta.

Myeloid-derived suppressor cells depletion may cause pregnancy loss via upregulating the cytotoxicity of decidual natural killer cells.

Problem: Maternal immune system tolerance to the semiallogeneic fetus is critical for a successful pregnancy. Studies have shown that myeloid-derived suppressor cells (MDSCs) play an important role in maintaining feto-maternal tolerance. However, the mechanisms remain poorly understood.

Differential gene expression profile in monocytic myeloid-derived suppressor cells at maternal-fetal interface in a mouse model of spontaneous abortion.

Abstractbackground: Monocytic myeloid-derived suppressor cells (MO-MDSCs) play an important role in maintaining normal pregnancy. However, it is still not clear what kind of changes in MO-MDSCs may lead to miscarriage, and which gene expression changes take place when MO-MDSCs migrate to the uterus as bone marrow-derived cells.

Methods: We used flow sorting technology to obtain MO-MDSCs from the maternal-fetal interface and bone marrow, respectively.

Plasmacytoma variant translocation 1 (PVT1) regulates trophoblast viability, proliferation, and migration and is downregulated in spontaneous abortion.

Problem: Human pregnancy is a complex biological process, and spontaneous abortion is the most common complication of pregnancy. LncRNAs have been identified that play key roles in a variety of human diseases. Recently, lncRNAPVT1 was reported to relate to the pathogenesis and progression of pregnancy.

EIF5A1 promotes trophoblast migration and invasion via ARAF-mediated activation of the integrin/ERK signaling pathway.

Trophoblast dysfunction is one mechanism implicated in the etiology of recurrent miscarriage (RM). Regulation of trophoblast function, however, is complex and the mechanisms contributing to dysregulation remain to be elucidated. Herein, we found EIF5A1 expression levels to be significantly decreased in cytotrophoblasts in RM villous tissues compared with healthy controls.

Elevated Tristetraprolin Impairs Trophoblast Invasion in Women with Recurrent Miscarriage by Destabilization of HOTAIR.

Tristetraprolin (TTP) regulates the stability of multiple targets that have important biological roles. However, the role of TTP in trophoblasts at the maternal-fetal interface remains poorly understood. We demonstrated that TTP was upregulated in placental trophoblasts from patients with recurrent miscarriages (RMs).

The activation of microRNA-520h-associated TGF-β1/c-Myb/Smad7 axis promotes epithelial ovarian cancer progression.

Among the gynaecological cancers, epithelial ovarian cancer (EOC) has the highest lethality because of the high incidence of tumour progression and metastasis. Exploration of the detailed mechanisms underlying EOC metastasis and the identification of crucial targets is important to better estimate the prognosis and improve the treatment of this disease. The present study aimed to identify the role of miR-520h in the prognosis of patients with EOC, and the mechanisms of its involvement in EOC progression.