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Background/Objectives: Chorionic villus sampling (CVS) is a pivotal diagnostic tool for early prenatal detection of chromosomal and genetic abnormalities; however, the safety and diagnostic efficacy of different CVS approaches remain a subject of clinical interest. This monocentric study compares transcervical (TC-CVS), transabdominal (TA-CVS) and transvaginal (TV-CVS) techniques, focusing on procedure-related fetal loss and diagnostic yield. Methods: In this 15-year, single-operator prospective study, a total of 5500 women underwent CVS between 10 and 14 weeks of gestation at a single center. Sampling was performed via TA-CVS (n = 4500), TC-CVS (n = 850), or TV-CVS (n = 150). Outcomes assessed included fetal loss rates, sample adequacy, early complications and hemodynamic changes measured by Doppler ultrasound. A p-value < 0.05 (two-tailed) was considered statistically significant. Results: Spontaneous abortion rates were significantly lower following TA-CVS (0.18%; 8/4500) compared to TC-CVS (0.6%; 5/850) and TV-CVS (1.3%; 2/150) (χ2 = 24.56, p < 0.001). Post hoc pairwise analysis showed significantly lower fetal loss in TA-CVS compared to TC-CVS, but not between TA-CVS and TV-CVS. Cytogenetic abnormalities were detected in 220 cases (4.0%), and clinically significant copy number variants (CNVs) were confirmed in fetuses with major structural malformations. Five-year follow-up showed no diagnosed intellectual disability among assessed children. Optimal tissue weight (10–20 mg) was more frequent with TA-CVS (66.7%) than TC-CVS (35.3%) or TV-CVS (36.7%) (χ2 = 350.92, p < 0.001). In a Doppler subset (n = 400), uterine, spiral, and interplacental artery PI changes were non-significant; the umbilical (p = 0.032) and middle cerebral arteries (p < 0.001) showed transient PI reductions after sampling. Conclusions: Transabdominal CVS demonstrated the most favorable balance of safety and diagnostic quality, suggesting it should be the preferred first-line technique in early prenatal diagnosis. Standardized technique and operator training remain critical to optimize outcomes.

Two-hundred-eighty-day-old broiler chicks were divided into seven groups. The groups were designated as T1, thermoneutral zone; T2, heat stressed (HS); T3, HS + zinc (Zn) supplementation (30 mg/kg); T4, HS + Zn (60 mg/kg); T5, HS + probiotic (0.1 g/kg); T6, HS + probiotic (0.1 g/kg) + Zn (30 mg/kg); and T7, HS + Zn (60 mg/kg) + probiotic (0.1 g/kg). Significant decrease ( p  < 0.05) was observed in villus height (VH), VH to crypt depth ratio, and villus surface area of all intestinal segments in the T2 group when compared with the T1 group. The same parameters had significantly higher ( p  < 0.05) values in the jejunum and ileum of the Zn- and probiotic-supplemented groups (alone + combination) when compared with the T2 group. The birds exposed to HS showed fewer ( p  < 0.05) intraepithelial lymphocytes (IELs) in the jejunum and ileum than the T1 group, while their count increased in the jejunum and ileum with dietary treatments. In conclusion, Zn and probiotic positively modulated the intestinal microstructures of broilers kept under high environmental temperature.

Cytosolic Malic Enzyme (ME1) provides reduced NADP for anabolism and maintenance of redox status. To examine the role of ME1 in tumor genesis of the gastrointestinal tract, we crossed mice having augmented intestinal epithelial expression of ME1 (ME1-Tg mice) with Apc Min/+ mice to obtain male Apc Min/+ /ME1-Tg mice. ME1 protein levels were significantly greater within gut epithelium and adenomas of male Apc Min/+ /ME1-Tg than Apc Min/+ mice. Male Apc Min/+ /ME1-Tg mice had larger and greater numbers of adenomas in the small intestine (jejunum and ileum) than male Apc Min/+ mice. Male Apc Min/+ /ME1-Tg mice exhibited greater small intestine crypt depth and villus length in non-adenoma regions, correspondent with increased KLF9 protein abundance in crypts and lamina propria . Small intestines of male Apc Min/+ /ME1-Tg mice also had enhanced levels of Sp5 mRNA, suggesting Wnt/β-catenin pathway activation. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro , but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.

The villus of the small intestine plays an essential role in the digestion and absorption of nutrients. They mix chyme with digestive secretions and absorb nutrients by assisting in food agitation and adherence in the intestinal lumen. The height of villi is a critical indicator of the effective absorptive area of the small intestine, which will be greatly reduced if the villi are shortened. Many factors influence the height of intestinal villi, including age, diet, disease, and environmental conditions. This review summarizes the common factors affecting intestinal villus height to provide theoretical guidelines for enhancing intestinal health.

The intestinal epithelium withstands continuous mechanical, chemical and biological insults despite its single-layered, simple epithelial structure. The crypt–villus tissue architecture in combination with rapid cell turnover enables the intestine to act both as a barrier and as the primary site of nutrient uptake. Constant tissue replenishment is fuelled by continuously dividing stem cells that reside at the bottom of crypts. These cells are nurtured and protected by specialized epithelial and mesenchymal cells, and together constitute the intestinal stem cell niche. Intestinal stem cells and early progenitor cells compete for limited niche space and, therefore, the ability to retain or regain stemness. Those cells unable to do so differentiate to one of six different mature cell types and move upwards towards the villus, where they are shed into the intestinal lumen after 3–5 days. In this Review, we discuss the signals, cell types and mechanisms that control homeostasis and regeneration in the intestinal epithelium. We investigate how the niche protects and instructs intestinal stem cells, which processes drive differentiation of mature cells and how imbalance in key signalling pathways can cause human disease.

Abnormal placentation is considered as an underlying cause of various pregnancy complications such as miscarriage, preeclampsia and intrauterine growth restriction, the latter increasing the risk for the development of severe disorders in later life such as cardiovascular disease and type 2 diabetes. Despite their importance, the molecular mechanisms governing human placental formation and trophoblast cell lineage specification and differentiation have been poorly unravelled, mostly due to the lack of appropriate cellular model systems. However, over the past few years major progress has been made by establishing self-renewing human trophoblast stem cells and 3-dimensional organoids from human blastocysts and early placental tissues opening the path for detailed molecular investigations. Herein, we summarize the present knowledge about human placental development, its stem cells, progenitors and differentiated cell types in the trophoblast epithelium and the villous core. Anatomy of the early placenta, current model systems, and critical key regulatory factors and signalling cascades governing placentation will be elucidated. In this context, we will discuss the role of the developmental pathways Wingless and Notch, controlling trophoblast stemness/differentiation and formation of invasive trophoblast progenitors, respectively.

Epithelial organoids, such as those derived from stem cells of the intestine, have great potential for modelling tissue and disease biology 1 , 2 , 3 – 4 . However, the approaches that are used at present to derive these organoids in three-dimensional matrices 5 , 6 result in stochastically developing tissues with a closed, cystic architecture that restricts lifespan and size, limits experimental manipulation and prohibits homeostasis. Here, by using tissue engineering and the intrinsic self-organization properties of cells, we induce intestinal stem cells to form tube-shaped epithelia with an accessible lumen and a similar spatial arrangement of crypt- and villus-like domains to that in vivo. When connected to an external pumping system, the mini-gut tubes are perfusable; this allows the continuous removal of dead cells to prolong tissue lifespan by several weeks, and also enables the tubes to be colonized with microorganisms for modelling host–microorganism interactions. The mini-intestines include rare, specialized cell types that are seldom found in conventional organoids. They retain key physiological hallmarks of the intestine and have a notable capacity to regenerate. Our concept for extrinsically guiding the self-organization of stem cells into functional organoids-on-a-chip is broadly applicable and will enable the attainment of more physiologically relevant organoid shapes, sizes and functions. Miniature gut tubes grown in vitro from mouse intestinal stem cells are perfusable, can be colonized with microorganisms and exhibit a similar arrangement and diversity of specialized cell types to intestines in vivo.

Fructose consumption is linked to the rising incidence of obesity and cancer, which are two of the leading causes of morbidity and mortality globally 1 , 2 . Dietary fructose metabolism begins at the epithelium of the small intestine, where fructose is transported by glucose transporter type 5 (GLUT5; encoded by SLC2A5 ) and phosphorylated by ketohexokinase to form fructose 1-phosphate, which accumulates to high levels in the cell 3 , 4 . Although this pathway has been implicated in obesity and tumour promotion, the exact mechanism that drives these pathologies in the intestine remains unclear. Here we show that dietary fructose improves the survival of intestinal cells and increases intestinal villus length in several mouse models. The increase in villus length expands the surface area of the gut and increases nutrient absorption and adiposity in mice that are fed a high-fat diet. In hypoxic intestinal cells, fructose 1-phosphate inhibits the M2 isoform of pyruvate kinase to promote cell survival 5 – 7 . Genetic ablation of ketohexokinase or stimulation of pyruvate kinase prevents villus elongation and abolishes the nutrient absorption and tumour growth that are induced by feeding mice with high-fructose corn syrup. The ability of fructose to promote cell survival through an allosteric metabolite thus provides additional insights into the excess adiposity generated by a Western diet, and a compelling explanation for the promotion of tumour growth by high-fructose corn syrup. A high-fructose diet in mice improves the survival of intestinal epithelial cells, which leads to an increase in gut surface area, enhanced absorption of lipids and the promotion of tumour growth and obesity.

Human intestinal morphogenesis establishes 3D epithelial microarchitecture and spatially organized crypt–villus characteristics. This unique structure is necessary to maintain intestinal homeostasis by protecting the stem cell niche in the basal crypt from exogenous microbial antigens and their metabolites. Also, intestinal villi and secretory mucus present functionally differentiated epithelial cells with a protective barrier at the intestinal mucosal surface. Thus, re-creating the 3D epithelial structure is critical to building in vitro intestine models. Notably, an organomimetic gut-on-a-chip can induce spontaneous 3D morphogenesis of an intestinal epithelium with enhanced physiological function and biomechanics. Here we provide a reproducible protocol to robustly induce intestinal morphogenesis in a microfluidic gut-on-a-chip as well as in a Transwell-embedded hybrid chip. We describe detailed methods for device fabrication, culture of Caco-2 or intestinal organoid epithelial cells in conventional setups as well as on microfluidic platforms, induction of 3D morphogenesis and characterization of established 3D epithelium using multiple imaging modalities. This protocol enables the regeneration of functional intestinal microarchitecture by controlling basolateral fluid flow within 5 d. Our in vitro morphogenesis method employs physiologically relevant shear stress and mechanical motions, and does not require complex cellular engineering or manipulation, which may be advantageous over other existing techniques. We envision that our proposed protocol may have a broad impact on biomedical research communities, providing a method to regenerate in vitro 3D intestinal epithelial layers for biomedical, clinical and pharmaceutical applications.The authors describe how to make both a gut-on-a-chip and a hybrid chip with a Transwell insert, and how to induce 3D morphogenesis of human intestinal epithelium from either Caco-2 cells or organoids using basolateral medium flow in both platforms.

Human placental villi have essential roles in producing hormones, mediating nutrient and waste exchange, and protecting the fetus from exposure to xenobiotics. Human trophoblast organoids that recapitulate the structure of villi could provide an important in vitro tool to understand placental development and the transplacental passage of xenobiotics. However, such organoids do not currently exist. Here we describe the generation of trophoblast organoids using human trophoblast stem (TS) cells. Following treatment with three kinds of culture medium, TS cells form spherical organoids with a single outer layer of syncytiotrophoblast (ST) cells that display a barrier function. Furthermore, we develop a column-type ST barrier model based on the culture condition of the trophoblast organoids. The bottom membrane of the column is almost entirely covered with syndecan 1-positive ST cells. The barrier integrity and maturation levels of the model are confirmed by measuring transepithelial/transendothelial electrical resistance (TEER) and the amount of human chorionic gonadotropin. Further analysis reveals that the model can be used to derive the apparent permeability coefficients of model compounds. In addition to providing a suite of tools for the study of placental development, our trophoblast models allow the evaluation of compound transfer and toxicity, which will facilitate drug development. The placenta is a transient organ that regulates the fetal environment, but our understanding of placental barrier function has been hampered by the lack of in vitro models. Here they develop human placental organoids that resemble the placental villus and form an intact syncytiotrophoblast barrier when cultured in a column model.