Single-cell assessment of primary and stem cell-derived human trophoblast organoids as placenta-modeling platforms.

Human trophoblast stem cells (hTSCs) and related trophoblast organoids are state-of-the-art culture systems that facilitate the study of trophoblast development and human placentation. Using single-cell transcriptomics, we evaluate how organoids derived from freshly isolated first-trimester trophoblasts or from established hTSC cell lines reproduce developmental cell trajectories and transcriptional regulatory processes defined in vivo. Although organoids from primary trophoblasts and hTSCs overall model trophoblast differentiation with accuracy, specific features related to trophoblast composition, trophoblast differentiation, and transcriptional drivers of trophoblast development show levels of misalignment.

Natural history of cardiac findings in mucopolysaccharidosis type I: report from an international registry.

Mucopolysaccharidosis type I is an inborn error of glycosaminoglycan catabolism with phenotypes ranging from severe (Hurler syndrome) to attenuated (Hurler-Scheie and Scheie syndromes). Cardiovascular involvement is common and contributes significantly to morbidity and mortality. We conducted a retrospective analysis of the prevalence and natural history of cardiac abnormalities in treatment-naïve individuals enrolled in the international Mucopolysaccharidosis Type I Registry.

Human organoid systems in modeling reproductive tissue development, function, and disease.

Research focused on human reproductive biology has primarily relied upon clinical samples affording mainly descriptive studies with limited implementation of functional or mechanistic understanding. More importantly, restricted access to human embryonic material has necessitated the use of animals, primarily rats and mice, and short-term primary cell cultures derived from human patient material. While reproductive developmental processes are generally conserved across mammals, specific features unique to human reproduction have resulted in the development of human-based in vitro systems designed to retain or recapitulate key molecular and cellular processes important in humans.

Transcriptomic mapping of the metzincin landscape in human trophoblasts.

The metzincin family of metalloproteases coordinates tissue developmental processes through regulation of growth factor availability, receptor signaling, and cell-cell/cell-matrix adhesion. While roles for select metzincins in controlling trophoblast functions in human placental development have been described, a comprehensive understanding of metzincin dynamics during trophoblast differentiation is lacking. To address this knowledge gap, single cell transcriptomic datasets derived from first trimester chorionic villi and decidua were used to decipher metzincin expression profiles and kinetics in diverse cell types within the utero-placental interface.

Growth in individuals with attenuated mucopolysaccharidosis type I during untreated and treated periods: Data from the MPS I registry.

Mucopolysaccharidosis Type I (MPS I) is caused by deficiency of α-L-iduronidase. Short stature and growth deceleration are common in individuals with the attenuated MPS I phenotype. Study objectives were to assess growth in individuals with attenuated MPS I enrolled in The MPS I Registry while untreated and after initiation of enzyme replacement therapy (ERT) with laronidase (recombinant human iduronidase).

Variability in the Follow-up Management of Pediatric Femoral Fractures.

Introduction: Variability in follow-up has previously been identified in orthopaedic trauma. Variability in follow-up for pediatric femur fractures has not previously been documented. The aim of this study was to document the variability in clinical and radiographic follow-up for pediatric femur fractures based on the fixation method and the treating surgeon.

Cell trajectory modeling identifies a primitive trophoblast state defined by BCAM enrichment.

In early placental development, progenitor cytotrophoblasts (CTB) differentiate along one of two cellular trajectories: the villous or extravillous pathways. CTB committed to the villous pathway fuse with neighboring CTB to form the outer multinucleated syncytiotrophoblast (SCT), whereas CTB committed to the extravillous pathway differentiate into invasive extravillous trophoblasts (EVT). Unfortunately, little is known about the processes controlling human CTB progenitor maintenance and differentiation.

The Role of Antenatal and Postnatal Maternal Bonding in Infant Development.

Objective: The affectional bond experienced by a mother toward her developing fetus/infant has been theorized to be a critical factor in determining infant developmental outcomes; yet there remains a paucity of research in this area, and a lack of high-quality longitudinal studies. This study aimed to examine the extent to which mother-to-infant bonding predicted infant development in a multi-wave longitudinal pregnancy cohort study (N = 1,347).

Method: Self-reported bonding was assessed using the Maternal Antenatal Attachment Scale at each trimester, and the Maternal Postnatal Attachment Scale at 8 weeks and 12 months postpartum.

Galectin-3 Modulates Microglia Inflammation in vitro but Not Neonatal Brain Injury in vivo under Inflammatory Conditions.

Microglia may contribute to injury but may also have neuroprotective properties. Galectin-3 has immunomodulatory properties that may affect the microglia phenotype and subsequent development of injury. Galectin-3 contributes to experimental hypoxic-ischemic (HI) injury in the neonatal brain, but it is unclear if galectin-3 has similar effects on infectious and sterile inflammation.

Maternal Obesity and the Uterine Immune Cell Landscape: The Shaping Role of Inflammation.

Inflammation is often equated to the physiological response to injury or infection. Inflammatory responses defined by cytokine storms control cellular mechanisms that can either resolve quickly (i.e.

Low oxygen enhances trophoblast column growth by potentiating differentiation of the extravillous lineage and promoting LOX activity.

Early placental development and the establishment of the invasive trophoblast lineage take place within a low oxygen environment. However, conflicting and inconsistent findings have obscured the role of oxygen in regulating invasive trophoblast differentiation. In this study, the effect of hypoxic, normoxic and atmospheric oxygen on invasive extravillous pathway progression was examined using a human placental explant model.

Lactating Canadian Women Consuming 1000 µg Folic Acid Daily Have High Circulating Serum Folic Acid Above a Threshold Concentration of Serum Total Folate.

Background: Consumption of high-dose folic acid supplements is common throughout pregnancy and lactation in several countries, including Canada, Brazil, and the United States, and may lead to high levels of circulating unmetabolized folic acid.

Objective: The objective of the study was to characterize serum and whole-blood folate forms in Canadian lactating women regularly consuming a daily high-dose folic acid supplement.

Methods: One-hundred and seventeen Canadian lactating women aged between 18 and 42 y, with a geometric mean ± SD prepregnancy body mass index (kg/m2) of 23.

Elevated Mitochondrial Reactive Oxygen Species and Cellular Redox Imbalance in Human NADPH-Oxidase-Deficient Phagocytes.

Chronic granulomatous disease (CGD) is caused by mutations in genes that encode the NADPH-oxidase and result in a failure of phagocytic cells to produce reactive oxygen species (ROS) this enzyme system. Patients with CGD are highly susceptible to infections and often suffer from inflammatory disorders; the latter occurs in the absence of infection and correlates with the spontaneous production of inflammatory cytokines. This clinical feature suggests that NADPH-oxidase-derived ROS are not required for, or may even suppress, inflammatory processes.