Patterns of trophoblast migration in deep uterine arteries in accreta placentation.

Introduction: During normal placentation, extravillous trophoblast (EVT) colonises and, in synergy with maternal leukocytes, transforms the walls of uterine spiral arteries in the decidua and inner myometrium. In placenta accreta spectrum (PAS), migration of extravillous trophoblasts (EVT) is abnormally deep, reaching larger upstream arteries in myometrium. As little is known about their interactions in accreta areas, scar tissue and deeper arteries were examined for colonisation and remodelling by trophoblast and maternal inflammatory cells.

Protein O-GlcNAcylation in reproductive biology and the impact of metabolic disease.

Background: Protein O-GlcNAcylation is a reversible post-translational modification which regulates the function of thousands of proteins to control generic and cell type-specific actions. O-GlcNAc addition and removal downstream of the hexosamine biosynthetic pathway (HBP) is mediated by only two enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA), respectively. Crucially, O-GlcNAcylation provides a regulatory layer to protein function that is responsive to metabolic status and thus metabolic disease impinges on this system.

Placenta accreta spectrum.

Placenta accreta spectrum is an increasingly common placental-related disorder diagnosed at birth when the placenta cannot be fully detached manually from the uterine wall, often requiring a surgical removal. Following a worldwide increase in caesarean delivery rates, more than 90% of cases are now found in patients with a history of caesarean delivery and an anterior low-lying placenta or a placenta previa. Accreta placentation is not a consequence of an inherently more aggressive cancer-like trophoblast but of a loss of the normal physiological cell signalling and physical regulatory mechanisms in the scar tissue, with higher-than-normal maternal blood velocity entering the intervillous space of the placenta, distortion of the corresponding lobules and a loss of the physiological site of detachment from the uterine wall.

NOTUM-mediated WNT silencing drives extravillous trophoblast cell lineage development.

Trophoblast stem (TS) cells have the unique capacity to differentiate into specialized cell types, including extravillous trophoblast (EVT) cells. EVT cells invade into and transform the uterus where they act to remodel the vasculature facilitating the redirection of maternal nutrients to the developing fetus. Disruptions in EVT cell development and function are at the core of pregnancy-related disease.

Glucose influences endometrial receptivity to embryo implantation through O-GlcNAcylation-mediated regulation of the cytoskeleton.

Phenotypic changes to endometrial epithelial cells underpin receptivity to embryo implantation at the onset of pregnancy but the effect of hyperglycemia on these processes remains poorly understood. Here, we show that physiological levels of glucose (5 mM) abolished receptivity in the endometrial epithelial cell line, Ishikawa. However, embryo attachment was supported by 17 mM glucose as a result of glucose flux through the hexosamine biosynthetic pathway (HBP) and modulation of cell function via protein O-GlcNAcylation.

Local vaginal bioelectrical impedance can predict preterm delivery in mice.

Preterm birth is a serious pregnancy complication that affects neonatal mortality, morbidity, and long-term neurological prognosis. Predicting spontaneous preterm delivery (PTD) is important for its management. While excluding the risk of PTD is important, identifying women at high risk of PTD is imperative for medical intervention.

NOTUM-MEDIATED WNT SILENCING DRIVES EXTRAVILLOUS TROPHOBLAST CELL LINEAGE DEVELOPMENT.

Trophoblast stem () cells have the unique capacity to differentiate into specialized cell types, including extravillous trophoblast () cells. EVT cells invade into and transform the uterus where they act to remodel the vasculature facilitating the redirection of maternal nutrients to the developing fetus. Disruptions in EVT cell development and function are at the core of pregnancy-related disease.

A systematic review of transcriptomic studies of the human endometrium reveals inconsistently reported differentially expressed genes.

Genome-wide analysis of gene expression has been widely applied to study the endometrium, although to our knowledge no systematic reviews have been performed. Here, we identified 74 studies that described transcriptomes from whole (unprocessed) endometrium samples and found that these fitted into three broad investigative categories; endometrium across the menstrual cycle, endometrium in pathology, and endometrium during hormone treatment. Notably, key participant information such as menstrual cycle length and body mass index was often not reported.

Endotheliochorial placental glycosylation reflects evolutionary divergence between Felidae species (Felis catus and Panthera leo) and Canidae (Canisfamiliaris).

Endotheliochorial cat (Felis catus) and lion (Panthera leo) term placentae and one 6 week placenta (term 60-63 days) from a dog (Canis familiaris) were stained with a panel of 24 lectins to compare glycosylation at the feto-maternal interface. Glycan expression in lion and cat placentae was very similar apart from the occurrence of terminal α-galactose in the lion trophoblast. The dog differed in several respects, particularly in the trophoblast, consistent with species-specific glycotypes differing according to the degree of their evolutionary divergence.

Lectin histochemistry reveals two cytotrophoblast differentiation pathways during placental development in the feline (Feliscatus).

Introduction: Placental glycosylation has been examined on eight feline placentae ranging from approximately 15 to 60 days post-conception as little is known about changes in glycan distribution in this species.

Methods: Specimens were resin embedded and lectin histochemistry was applied to semi-thin sections using a panel of 24 lectins and an avidin-biotin revealing system.

Results: Abundant tri-tetraantennary complex N-glycan and α-galactosyl residues found in the syncytium in early pregnancy were greatly reduced in mid-pregnancy, though retained at the invasion front in the syncytium (N-glycan) or cytotrophoblast layer (αGal).

Use of 'omics for endometrial timing: the cycle moves on.

For some years, the prospect of precise and personalized timing of the endometrial cycle for optimal embryo replacement has been held out as a potential solution to low implantation rates. It is envisaged that a receptive state can be defined and reached at a predictable time, and embryo replacement performed in synchrony. In the last century, morphological changes characteristic of the mid secretory phase were defined in precisely timed cycles in women of proven fertility, but when deviations from this standardized schedule occur, their significance for implantation has remained uncertain.

Trophectoderm differentiation to invasive syncytiotrophoblast is promoted by endometrial epithelial cells during human embryo implantation.

Study Question: How does the human embryo breach the endometrial epithelium at implantation?

Summary Answer: Embryo attachment to the endometrial epithelium promotes the formation of multinuclear syncytiotrophoblast from trophectoderm, which goes on to breach the epithelial layer.

What Is Known Already: A significant proportion of natural conceptions and assisted reproduction treatments fail due to unsuccessful implantation. The trophectoderm lineage of the embryo attaches to the endometrial epithelium before breaching this barrier to implant into the endometrium.

Intersection of regulatory pathways controlling hemostasis and hemochorial placentation.

Hemochorial placentation is characterized by the development of trophoblast cells specialized to interact with the uterine vascular bed. We utilized trophoblast stem (TS) cell and mutant rat models to investigate regulatory mechanisms controlling trophoblast cell development. TS cell differentiation was characterized by acquisition of transcript signatures indicative of an endothelial cell-like phenotype, which was highlighted by the expression of anticoagulation factors including tissue factor pathway inhibitor (TFPI).

Targeted Delivery of Epidermal Growth Factor to the Human Placenta to Treat Fetal Growth Restriction.

Placental dysfunction is the underlying cause of pregnancy complications such as fetal growth restriction (FGR) and pre-eclampsia. No therapies are available to treat a poorly functioning placenta, primarily due to the risks of adverse side effects in both the mother and the fetus resulting from systemic drug delivery. The use of targeted liposomes to selectively deliver payloads to the placenta has the potential to overcome these issues.

Altered protein O-GlcNAcylation in placentas from mothers with diabetes causes aberrant endocytosis in placental trophoblast cells.

Women with pre-existing diabetes have an increased risk of poor pregnancy outcomes, including disordered fetal growth, caused by changes to placental function. Here we investigate the possibility that the hexosamine biosynthetic pathway, which utilises cellular nutrients to regulate protein function via post-translationally modification with O-linked N-acetylglucosamine (GlcNAc), mediates the placental response to the maternal metabolic milieu. Mass spectrometry analysis revealed that the placental O-GlcNAcome is altered in women with type 1 (n = 6) or type 2 (n = 6) diabetes T2D (≥ twofold change in abundance in 162 and 165 GlcNAcylated proteins respectively compared to BMI-matched controls n = 11).

A re-examination of the origins of placental bed giant cells.

In view of controversy about the source of placental multinuclear giant cells, we have re-examined the literature which clearly shows they are derived from trophoblastic elements that have populated the decidua. Archival material for electron microscopy from 17 to 18 week placentae demonstrates they can be found connected via desmosomes to the outer extravillous cytotrophoblast cells of anchoring columns, thus identifying a primary source. We suggest their formation is a terminal differentiation step occurring at all stages of invasion from the cell column to the myometrium, progressively reducing the invasive population.

Cell dynamics in human villous trophoblast.

Background: Villous cytotrophoblast (vCTB) is a precursor cell population that supports the development of syncytiotrophoblast (vSTB), the high surface area barrier epithelium of the placental villus, and the primary interface between maternal and fetal tissue. In light of increasing evidence that the placenta can adapt to changing maternal environments or, under stress, can trigger maternal disease, we consider what properties of these cells empower them to exert a controlling influence on pregnancy progression and outcome.

Objective And Rationale: How are cytotrophoblast proliferation and differentiation regulated in the human placental villus to allow for the increasing demands of the fetal and environmental challenges and stresses that may arise during pregnancy?

Search Methods: PubMed was interrogated using relevant keywords and word roots combining trophoblast, villus/villous, syncytio/syncytium, placenta, stem, transcription factor (and the individual genes), signalling, apoptosis, autophagy (and the respective genes) from 1960 to the present.

ASCL2 reciprocally controls key trophoblast lineage decisions during hemochorial placenta development.

Invasive trophoblast cells are critical to spiral artery remodeling in hemochorial placentation. Insufficient trophoblast cell invasion and vascular remodeling can lead to pregnancy disorders including preeclampsia, preterm birth, and intrauterine growth restriction. Previous studies in mice identified achaete-scute homolog 2 (ASCL2) as essential to extraembryonic development.

A preliminary study on the glycosylation of the reproductive tract in the Ostrich (Struthio camelus camelus).

Glycosylation of the reproductive tract of an adult female red-necked ostrich (Struthio camelus camelus) carrying a fully formed calcified egg in her uterus when accidently killed by a blow to the head was examined using lectin histochemistry on samples from the infundibulum, magnum, uterus and vagina. Glycans in the luminal epithelium and underlying glands were described after staining with 23 lectins after neuraminidase pre-treatment in some cases. Ciliated and non-ciliated cells were evident at all levels in the luminal epithelium, the latter full of richly glycosylated secretory granules.

Protein O-GlcNAcylation Promotes Trophoblast Differentiation at Implantation.

Embryo implantation begins with blastocyst trophectoderm (TE) attachment to the endometrial epithelium, followed by the breaching of this barrier by TE-derived trophoblast. Dynamic protein modification with O-linked β-N-acetylglucosamine (O-GlcNAcylation) is mediated by O-GlcNAc transferase and O-GlcNAcase (OGA), and couples cellular metabolism to stress adaptation. O-GlcNAcylation is essential for blastocyst formation, but whether there is a role for this system at implantation remains unexplored.

Tracking placental development in health and disease.

Pre-eclampsia and fetal growth restriction arise from disorders of placental development and have some shared mechanistic features. Initiation is often rooted in the maldevelopment of a maternal-placental blood supply capable of providing for the growth requirements of the fetus in later pregnancy, without exerting undue stress on maternal body systems. Here, we review normal development of a placental bed with a safe and adequate blood supply and a villous placenta-blood interface from which nutrients and oxygen can be extracted for the growing fetus.

The influences of cycle stage and pregnancy upon cell glycosylation in the endometrium of the mare.

From Day 6.5-7 post-conception until its loss around Day 22, the equine embryo is enclosed in a mucinous capsule that prevents direct intercellular interaction between the trophectoderm and uterine epithelium. The embryo is, however, bathed in glycoprotein-rich secretions.