The therapeutic effects of vitamin D3 administration on the embryo implantation.

Various adjuvants have been tested clinically for patients with problems with embryo implantation during in vitro fertilization (IVF)-embryo transfer (ET). Vitamin D3, an essential modulator of various physiological processes, has received attention as an important adjuvant for successful pregnancy, as many studies have shown a strong association between vitamin D deficiency and implantation failure and fetal growth restriction. However, vitamin D has been widely utilized in different protocols, resulting in non-reproducible and debatable outcomes.

Endometrial organoids: a reservoir of functional mitochondria for uterine repair.

Asherman's syndrome (AS) is a dreadful gynecological disorder of the uterus characterized by intrauterine adhesion with severe fibrotic lesions, resulting in a damaged basalis layer with infertility. Despite extensive research on overcoming AS, evidence-based effective and reproducible treatments to improve the structural and functional morphology of the AS endometrium have not been established. Endometrial organoids generated from human or mouse endometrial tissues were transplanted into the uterine cavity of a murine model of AS to evaluate their transplantable feasibility to improve the AS uterine environment.

Fabrication of Partially Etched Polystyrene Nanoparticles.

Non-spherical polymer nanoparticles (NPs) have gained attention in various fields, but their fabrication remains challenging. In this study, we present a simple protocol for synthesizing partially etched polystyrene (PS) nanoparticles through emulsion polymerization and chemical etching. By adjusting the degree of crosslinking, we selectively dissolve the weakly crosslinked portions of the particles, resulting in partially etched PS NPs with increased surface area.

The therapeutic effects and optimal timing of granulocyte colony stimulating factor intrauterine administration during IVF-ET.

Most of embryos fail to produce live offspring during In Vitro Fertilization-Embryo Transfer (IVF-ET) procedure. There is a dearth of research activity addressing this problem despite the significant population of women suffering from repeated implantation failure after transfer of high-quality of embryos. As a clinically accessible option, granulocyte colony stimulating factor (G-CSF) is often used for the treatment to improve the rates of embryo implantation.

Intrauterine botulinum toxin A administration promotes endometrial regeneration mediated by IGFBP3-dependent OPN proteolytic cleavage in thin endometrium.

Adequate endometrial growth is a critical factor for successful embryo implantation and pregnancy maintenance. We previously reported the efficacy of intrauterine administration of botulinum toxin A (BoTA) in improving the endometrial angiogenesis and the rates of embryo implantation. Here, we further evaluated its potent therapeutic effects on the uterine structural and functional repair and elucidated underlying molecular regulatory mechanisms.

Accumulated Vitrified Embryos Could Be a Method for Increasing Pregnancy Rates in Patients with Poor Ovarian Response.

We aimed to assess the efficacy of accumulated embryo transfer (ACC-ET) through several controlled ovarian hyperstimulation (COS) cycles to increase the rates of pregnancy in patients with poor ovarian response (POR). We retrospectively reviewed the medical records of 588 patients with POR under 43-years old who underwent embryo transfer from January 2010 to December 2015. We compared the pregnancy rate (PR), clinical pregnancy rate (CPR), and live birth rate (LBR) between ACC-ET (frozen-thawed: 47; fresh + frozen-thawed: 24) group (n = 71) and fresh ET groups (n = 517).

Effects of Elevated Progesterone Levels on the Day of hCG on the Quality of Oocyte and Embryo.

This study is designed to investigate the effects of increased progesterone (P4) levels on the quality of retrieved oocytes and embryos during IVF. This retrospective analysis included 982 all-freezing in vitro fertilization (IVF) cycles (conducted between November 2019 and June 2020 at CHA Fertility Center Bundang, South Korea) in which serum P4 levels were measured on the day of human chorionic gonadotropin (hCG) administration. Our study revealed that the serum P4 levels on the day of hCG administration are strongly associated with the rates of oocyte maturation, displaying a positive correlation in patients with serum P4 < 2.

A new method for obtaining bankable and expandable adult-like microglia in mice.

Background: The emerging role of microglia in neurological disorders requires a novel method for obtaining massive amounts of adult microglia. We aim to develop a new method for obtaining bankable and expandable adult-like microglia in mice.

Methods: The head neuroepithelial layer (NEL) that composed of microglial progenitor and neuroepithelial cells at mouse E13.

Dysfunctional activity of classical DNA end-joining renders acquired resistance to carboplatin in human ovarian cancer cells.

Ovarian cancer is the deadliest gynecological malignancy worldwide. Although chemotherapy is required as the most standard treatment strategy for ovarian cancer, the survival rates are very low, largely because of high incidence of recurrence due to resistance to conventional surgery and genotoxic chemotherapies. Carboplatin-resistant ovarian cancer cells were generated by continuous treatment over six months.

Three-dimensional microengineered vascularised endometrium-on-a-chip.

Study Question: Can we reconstitute physiologically relevant 3-dimensional (3D) microengineered endometrium in-vitro model?

Summary Answer: Our representative microengineered vascularised endometrium on-a-chip closely recapitulates the endometrial microenvironment that consists of three distinct layers including epithelial cells, stromal fibroblasts and endothelial cells in a 3D extracellular matrix in a spatiotemporal manner.

What Is Known Already: Organ-on-a-chip, a multi-channel 3D microfluidic cell culture system, is widely used to investigate physiologically relevant responses of organ systems.

Study Design, Size, Duration: The device consists of five microchannels that are arrayed in parallel and partitioned by array of micropost.

CXCL12 enhances pregnancy outcome via improvement of endometrial receptivity in mice.

Successful pregnancy inevitably depends on the implantation of a competent embryo into a receptive endometrium. Although many substances have been suggested to improve the rate of embryo implantation targeting enhancement of endometrial receptivity, currently there rarely are effective evidence-based treatments to prevent or cure this condition. Here we strongly suggest minimally-invasive intra-uterine administration of embryo-secreted chemokine CXCL12 as an effective therapeutic intervention.

Non-invasive Intrauterine Administration of Botulinum Toxin A Enhances Endometrial Angiogenesis and Improves the Rates of Embryo Implantation.

Endometrial angiogenesis plays crucial roles in determining the endometrial receptivity. Defects in endometrial receptivity often cause repeated implantation failure, which is one of the major unmet needs for infertility and contributes a major barrier to the assisted reproductive technology. Despite the numerous extensive research work, there are currently no effective evidence-based treatments to prevent or cure this condition.

Profilin-1; a novel regulator of DNA damage response and repair machinery in keratinocytes.

Profilin-1 (PFN1) regulates actin polymerization and cytoskeletal growth. Despite the essential roles of PFN1 in cell integration, its subcellular function in keratinocyte has not been elucidated yet. Here we characterize the specific regulation of PFN1 in DNA damage response and repair machinery.

miR-4463 regulates aromatase expression and activity for 17β-estradiol synthesis in response to follicle-stimulating hormone.

Objective: The aim of this study was to investigate microRNAs (miRNAs) related to follicle-stimulating hormone (FSH) responsiveness using miRNA microarrays and to identify their target genes to determine the molecular regulatory pathways involved in FSH signaling in KGN cells.

Methods: To change the cellular responsiveness to FSH, KGN cells were treated with FSH receptor (FSHR)-specific small interfering RNA (siRNA) followed by FSH. miRNA expression profiles were determined through miRNA microarray analysis.

Endometrial profilin 1: a key player in embryo-endometrial crosstalk.

Objective: Despite extensive research on implantation failure, little is known about the molecular mechanisms underlying the crosstalk between the embryo and the maternal endometrium, which is critical for successful pregnancy. Profilin 1 (PFN1), which is expressed both in the embryo and in the endometrial epithelium, acts as a potent regulator of actin polymerization and the cytoskeletal network. In this study, we identified the specific role of endometrial PFN1 during embryo implantation.

Eupatilin treatment inhibits transforming growth factor beta-induced endometrial fibrosis in vitro.

Objective: Endometrial fibrosis, the primary pathological feature of intrauterine adhesion, may lead to disruption of endometrial tissue structure, menstrual abnormalities, infertility, and recurrent pregnancy loss. At present, no ideal therapeutic strategy exists for this fibrotic disease. Eupatilin, a major pharmacologically active flavone from Artemisia, has been previously reported to act as a potent inducer of dedifferentiation of fibrotic tissue in the liver and lung.

Corrigendum: Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival.

This corrects the article DOI: 10.1038/ncomms14013.

Contribution of classical end-joining to PTEN inactivation in p53-mediated glioblastoma formation and drug-resistant survival.

DNA repair gene defects are found in virtually all human glioblastomas, but the genetic evidence for a direct role remains lacking. Here we demonstrate that combined inactivation of the XRCC4 non-homologous end-joining (NHEJ) DNA repair gene and p53 efficiently induces brain tumours with hallmark characteristics of human proneural/classical glioblastoma. The murine tumours exhibit PTEN loss of function instigated by reduced PTEN mRNA, and increased phosphorylated inactivation and stability as a consequence of aberrantly elevated CK2 provoked by p53 ablation and irrevocably deregulated by NHEJ inactivation.

MiR-145 suppresses embryo-epithelial juxtacrine communication at implantation by modulating maternal IGF1R.

Successful implantation requires the synchronization of viable embryonic development with endometrial receptivity. The mechanisms allowing for the initiation of crosstalk between the embryo and the endometrium remain elusive; however, recent studies have revealed that there are alterations in endometrial microRNAs (miRs) in women suffering repeated implantation failure and that one of the altered miRs is miR-145. We assessed the role of miR-145 and its target IGF1R, in early implantation.

Suppression of T-cell lymphomagenesis in mice requires PTEN phosphatase activity.

Mice with T-cell-specific loss of the tumor suppressor gene PTEN early in T-cell ontogeny develop thymic lymphomas that invariably harbor a reciprocal translocation involving the T-cell receptor α/δ locus and c-myc, t(14;15). In addition to its known function as a lipid phosphatase opposing PI3K signaling, PTEN has also been described as playing a prominent role in promoting genomic stability. As a result, it has been uncertain which one(s) of these 2 separable features were required to block the development of lymphoma.

Azilsartan is associated with increased circulating angiotensin-(1-7) levels and reduced renovascular 20-HETE levels.

Background: Activation of angiotensin (ANG) II type 1 receptors (AT1R) promotes vasoconstriction, inflammation, and renal dysfunction. In this study, we addressed the ability of azilsartan (AZL), a new AT1R antagonist, to modulate levels of plasma ANG-(1-7) and renal epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE).

Methods: Sprague-Dawley rats were infused with ANG II (125 ng/min) or vehicle (VEH).

The role of the osteopontin-integrin αvβ3 interaction at implantation: functional analysis using three different in vitro models.

Study Question: Does the interaction between integrin and its ligand osteopontin (OPN) mediate embryonic attachment to endometrial epithelium at implantation?

Summary Answer: OPN of epithelial origin binds the receptor integrin αvβ3 at the maternal surface to support adhesion during the early stages of implantation.

What Is Known Already: Integrin αvβ3 and OPN are both present in the endometrial luminal epithelium in the mid-secretory phase.

Study Design, Size, Duration: Microscopy of attachment sites of blastocysts (mouse, n = 151, human, n = 8) and OPN- or BSA-coated beads (n = 488) interacting with Ishikawa cell monolayers at 24 and 48 h.

MET signaling regulates glioblastoma stem cells.

Glioblastomas multiforme (GBM) contain highly tumorigenic, self-renewing populations of stem/initiating cells [glioblastoma stem cells (GSC)] that contribute to tumor propagation and treatment resistance. However, our knowledge of the specific signaling pathways that regulate GSCs is limited. The MET tyrosine kinase is known to stimulate the survival, proliferation, and invasion of various cancers including GBM.