Development of the smooth muscle layer in the ileum of mouse embryos.

The smooth muscle layer (SML) comprises a significant portion of the intestines and other tubular organs. Whereas epithelial development has recently been extensively studied, SML development has drawn relatively less attention. Previous morphological reports revealed that the inner circular layer (IC) differentiates earlier than the outer longitudinal layer (OL), but detailed development of the SML, including chronological changes in the cell layer number, precise cell orientation, and regional differences in relation to the mesentery, has not been reported. We here observed the development of the SML in the C57BL/6J mouse ileum near the ileocecal junction at embryonic day (E) 13.5, 15.5, and 17.5. By histo-morphometric analyses, in IC, smooth muscle cells (SMCs) were oval-shaped and irregularly arranged in 3-4 layers at E13.5, then adopted an elongated spindle shape and decreased to two cell layers at E15.5 and E17.5. The IC SMC nuclear angle was not vertical, but oriented at 60-80° against the mid-axis of the intestinal lumen. The single SMC layer in OL was observed at E17.5, and the SMC nuclear angle was parallel to the luminal mid-axis. No clear regional difference against the mesentery was observed. Collectively, the findings suggest that development and differentiation of the ileal SML is not simple but regulated in a complex manner and possibly related to the macroscopic organogenesis.

The EXTrauterine Environment for Neonatal Development Supports Normal Intestinal Maturation and Development.

BACKGROUND AND AIMS: The Extra-Uterine Environment for Neonatal Development (EXTEND) aims to avoid the complications of prematurity, such as NEC. Our goal was to determine if bowel development occurs normally in EXTEND-supported lambs, with specific emphasis on markers of immaturity associated with NEC. METHODS: We compared terminal ileum from 17 pre-term lambs supported on EXTEND for 2- 4 weeks to bowel from age-matched fetal lambs that developed in utero. We evaluated morphology, markers of epithelial integrity and maturation, enteric nervous system structure, and bowel motility. RESULTS: EXTEND-supported lamb ileum had normal villus height, crypt depth, density of mucin-containing goblet cells, and enteric neuron density. Expression patterns for I-FABP, activated caspase-3 and EGFR were normal in bowel epithelium. Transmural resistance assessed in Ussing chambers was normal. Bowel motility was also normal as assessed by ex vivo organ bath and video imaging. However, Peyer's patch organization did not occur normally in EXTEND ileum, resulting in fewer circulating B cells in experimental animals. CONCLUSION: EXTEND supports normal ileal epithelial and enteric nervous system maturation in pre-term lambs. The classic morphologic changes and cellular expression profiles associated with NEC are not seen. However, immune development within the EXTEND supported lamb bowel does not progress normally.

Organogenesis of Ileal Peyer's Patches Is Initiated Prenatally and Accelerated Postnatally With Comprehensive Proliferation of B Cells in Pigs.

Morphogenesis and differentiation of organs is required for subsequent functional maturation. The morphological features of Peyer's patches vary among species. In pigs, they develop extensively in the ileum as ileal Peyer's patches (IPPs). However, the role of IPPs in the porcine immune system remains to be elucidated because of a lack of complete understanding of IPP organogenesis. Results of the present study revealed that development of porcine IPPs is initiated prenatally between embryonic days 76 and 91. The process of IPP organogenesis is concomitant with increased transcriptional patterns of CXCL13 and CCL19. IPPs undergo further development postnatally by forming central, marginal, and subepithelial zones. Importantly, a large number of proliferating B cells and apoptotic cells are found in porcine IPPs postnatally, but not prenatally. The expression level of IgM in proliferating B cells depends on the zone in which distinct B cells are separately localized after birth. Specifically, IgM+ cells are predominantly found in the central zone, whereas IgM-/low cells are abundant in the marginal zone. Importantly, the cellular feature of IPPs differs from that of mesenteric lymph nodes (MLNs) where such distinct zones are not formed both prenatally and postnatally. Our findings suggest that IPPs (not MLNs) in postnatal pigs are involved in complementing functions of the primary lymphoid tissue that promotes the differentiation and maturation of B cells.

Lysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.

The guts of neonatal mammals and stomachless fish have a limited capacity for luminal protein digestion, which allows oral acquisition of antibodies and antigens. However, how dietary protein is absorbed during critical developmental stages when the gut is still immature is unknown. Here, we show that specialized intestinal cells, which we call lysosome-rich enterocytes (LREs), internalize dietary protein via receptor-mediated and fluid-phase endocytosis for intracellular digestion and trans-cellular transport. In LREs, we identify a conserved endocytic machinery, composed of the scavenger receptor complex Cubilin/Amnionless and Dab2, that is required for protein uptake by LREs and for growth and survival of larval zebrafish. Moreover, impairing LRE function in suckling mice, via conditional deletion of Dab2, leads to stunted growth and severe protein malnutrition reminiscent of kwashiorkor, a devastating human malnutrition syndrome. These findings identify digestive functions and conserved molecular mechanisms in LREs that are crucial for vertebrate growth and survival.

Abundance and Significance of Neuroligin-1 and Neurexin II in the Enteric Nervous System of Embryonic Rats.

Aim. To investigate the abundance of neuroligin-1 and neurexin II in the enteric nervous system (ENS) of rats on different embryonic days and to explore their potential significance. Methods. The full-thickness colon specimens proximal to the ileocecal junction of rats on embryonic days 16, 18, and 20 and of newborns within 24 hours (E16, E18, E20, and Ep0) were studied, respectively. qRT-PCR was applied for detecting the expressions of neuroligin-1 and neurexin II on mRNA, and western blotting was employed for detecting their further expressions on the whole tissue. Finally, the histological appearance of neuroligin-1 and neurexin IIα was elucidated using immunohistochemical staining. Results. qRT-PCR showed that the neuroligin-1 and neurexin II mRNA expressions of groups E16, E18, E20, and Ep0 increased gradually with the growth of embryonic rats (P < 0.05). Western blotting confirmed the increasing tendency. In immunohistochemical staining, proteins neuroligin-1 and neurexin IIα positive cells concentrated mostly in the myenteric nerve plexus of the colon and their expressions depend on the embryonic time. Conclusion. Neuroligin-1 and neurexin II were both expressed in the ENS and have temporal correlation with the development of ENS, during which neuronal intestinal malformations (NIM) may occur due to their disruptions and consequent abnormal ENS development.

Paneth cells in the developing gut: when do they arise and when are they immune competent?

BACKGROUND: Little is known about the perinatal development of Paneth cells (PCs) during gestation and the relation with necrotizing enterocolitis (NEC). We aimed to investigate when PCs arise and when they become immune competent during gestation. METHODS: We included 57 samples of ileum tissue of fetuses/infants with a gestional age (GA) between 9 and 40 wk taken as part of a standard autopsy procedure. Hematoxylin-eosin staining and anti-human defensin 5 immunohistochemistry were performed. We performed a semi-quantitative assessment of (immune-competent) PC numbers per 10 crypts per tissue section per GA. RESULTS: The number of PCs and the number of immune-competent PCs increased with increasing GA (Spearman's ρ = 0.41, P = 0.002 and ρ = 0.61, P < 0.001, respectively). Whereas significantly higher PC numbers were observed after 37 wk gestation (median 7, range 0-12) compared to preterm infants (median 0, range 0-15; P = 0.002), we counted higher numbers of immune-competent PCs already in infants with GA above 29 wk (median 6, range 0-18) compared to infants with GA under 29 wk (median 2, range 0-9; P < 0.001). CONCLUSION: The significant increase of immune-competent PCs starting from a GA of 29 wk mimics the rise in incidence of NEC during a similar postmenstrual age in preterm infants.

Hydrocortisone-induced anti-inflammatory effects in immature human enterocytes depend on the timing of exposure.

The immature human gut has a propensity to exaggerated inflammatory responses that are thought to play a role in the pathogenesis of necrotizing enterocolitis (NEC). Prenatal exposure to corticosteroids has been reported to reduce the risk of NEC, while postnatal dexamethasone treatment is associated with adverse neurodevelopmental outcomes in preterm infants. The aim of this study was to investigate the direct role of hydrocortisone in gene expression patterns and inflammatory responses in immature human enterocytes. Time-dependent hydrocortisone effects in nontransformed primary human fetal intestinal epithelial cell line H4 were investigated by cDNA microarray. Fetal intestinal organ culture and cell culture experiments were conducted. Inflammatory responses were induced by stimulation with IL-1ß and TNF-α with and without hydrocortisone. IL-8 and IL-6 expression and secretion were measured as functional readout. Here we report time-dependent hydrocortisone-induced changes in gene expression patterns detected by cDNA microarray. Hydrocortisone significantly attenuated IL-1ß-induced inflammatory responses in the immature human gut when administered at the time of the proinflammatory insult: IL-1ß-induced IL-8 and IL-6 secretion in the fetal ileum as well as H4 cells were significantly reduced. Hydrocortisone also inhibited IL-8 secretion in response to TNF-α. In contrast, TNF-α-induced IL-8 secretion was not reduced in cells treated with hydrocortisone for 48 h before stimulation. Our observations provide a physiological basis for understanding the differential clinical effects of corticosteroids in the immature human gut depending on the timing of treatment.

Long-chain polyunsaturated fatty acids attenuate the IL-1ß-induced proinflammatory response in human fetal intestinal epithelial cells.

BACKGROUND: Evidence suggests that excessive inflammation of the immature intestine may predispose premature infants to necrotizing enterocolitis (NEC). We investigated the anti-inflammatory effects of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and arachidonic acid (ARA) in human fetal and adult intestinal epithelial cells (IEC) in primary culture. METHODS: Human fetal IEC in culture were derived from a healthy fetal small intestine (H4) or resected small intestine of a neonate with NEC (NEC-IEC). Intestinal cell lines Caco2 and NCM460 in culture were used as models for mature IEC. IEC in culture were pretreated with 100 µmol/l palmitic acid (PAL), DHA, EPA, ARA, or ARA+DHA for 48 h and then stimulated with proinflammatory IL-1ß. RESULTS: DHA significantly attenuated IL-1ß induced proinflammatory IL-8 and IL-6 protein and mRNA in fetal H4, NEC-IEC, and mature Caco2, NCM460 IEC, compared to control and PAL treatment. DHA downregulated IL-1R1 (IL-1ß receptor) and NFk ß1 mRNA expression in fetal and adult IEC. ARA had potent anti-inflammatory effects with lower IL-8 and IL-6 (protein and mRNA) in fetal H4 but not in NEC-IEC or adult IEC. CONCLUSION: The present study provides evidence that DHA and ARA may have important anti-inflammatory functions for prevention of NEC in premature infants.

Lactobacillus rhamnosus GG and its SpaC pilus adhesin modulate inflammatory responsiveness and TLR-related gene expression in the fetal human gut.

BACKGROUND: Bacterial contact in utero modulates fetal and neonatal immune responses. Maternal probiotic supplementation reduces the risk of immune-mediated disease in the infant. We investigated the immunomodulatory properties of live Lactobacillus rhamnosus GG and its SpaC pilus adhesin in human fetal intestinal models. METHODS: Tumor necrosis factor (TNF)-α mRNA expression was measured by qPCR in a human fetal intestinal organ culture model exposed to live L. rhamnosus GG and proinflammatory stimuli. Binding of recombinant SpaC pilus protein to intestinal epithelial cells (IECs) was assessed in human fetal intestinal organ culture and the human fetal intestinal epithelial cell line H4 by immunohistochemistry and immunofluorescence, respectively. TLR-related gene expression in fetal ileal organ culture after exposure to recombinant SpaC was assessed by qPCR. RESULTS: Live L. rhamnosus GG significantly attenuates pathogen-induced TNF-α mRNA expression in the human fetal gut. Recombinant SpaC protein was found to adhere to the fetal gut and to modulate varying levels of TLR-related gene expression. CONCLUSION: The human fetal gut is responsive to luminal microbes. L. rhamnosus GG significantly attenuates fetal intestinal inflammatory responses to pathogenic bacteria. The L. rhamnosus GG pilus adhesin SpaC binds to immature human IECs and directly modulates IEC innate immune gene expression.

Accuracy of prenatal ultrasound in detecting jejunal and ileal atresia: systematic review and meta-analysis.

OBJECTIVE: The accuracy of prenatal ultrasound examination in detecting jejunal and ileal atresia has been reported in the literature to be highly variable, at 25-90%. The aim of this systematic review was to evaluate the accuracy of prenatal ultrasound in detecting non-duodenal small bowel atresia (ND-SBA). METHODS: MEDLINE, EMBASE and The Cochrane Library, including The Cochrane Database of Systematic Reviews (CDSR), Database of Abstracts of Reviews of Effects (DARE) and The Cochrane Central Register of Controlled Trials (CENTRAL), were searched electronically. The overall detection rate of jejunal or ileal atresia using ultrasound was reported. The accuracy of using polyhydramnios and dilated loops of bowel as diagnostic signs was also explored. RESULTS: Sixteen studies involving 640 fetuses were included in this review. The detection rate of ND-SBA by prenatal ultrasound was highly variable, with values ranging from 10 to 100%, with an overall prediction of 50.6% (95% CI, 38.0-63.2%). When analyzed separately, the detection rates of jejunal and ileal atresia were 66.3%, (95% CI, 33.9-91.8%) and 25.9% (95% CI, 4.0-58.0%), respectively. Both dilated loops of bowel and polyhydramnios as diagnostic signs for ND-SBA provided a low overall detection rate. CONCLUSIONS: The diagnostic performance of prenatal ultrasound in identifying ND-SBA is extremely variable. Large studies are needed in order to identify objective and combined criteria for the diagnosis of these anomalies.

Prenatal diagnosis of the acute meconium peritonitis secondary to ileum volvulus perforation: a case report.

This is an unusual case in comparison to other sonographically described prenatal cases due to very early diagnosis and surgical intervention following prompt delivery. A 40-year-old pregnant, ultrasonography showed presence of cystic structure in the fetal abdomen that was consistent with intestinal dilatation. At 32 weeks' of gestation, repeat ultrasound showed collapse of the bowel dilatation along with the presence of hyperechogenic fluid in the fetal abdominal cavity. Cesarean section was performed. The clinical utility of this report is the recognition that meconium peritonitis (MP) may be diagnosed in the acute phase with typical ultrasound features, and should be considered in the differential diagnoses of cases presented with reduced fetal movements. Although it appears that morbidity and mortality in MP cases depend upon gestational age, this case report may help to manage similar cases for defining the appropriate delivery time and treatment modality after prenatal identification of the problem.

Chorioamnionitis-induced fetal gut injury is mediated by direct gut exposure of inflammatory mediators or by lung inflammation.

Intra-amniotic exposure to proinflammatory agonists causes chorioamnionitis and fetal gut inflammation. Fetal gut inflammation is associated with mucosal injury and impaired gut development. We tested whether this detrimental inflammatory response of the fetal gut results from a direct local (gut derived) or an indirect inflammatory response mediated by the chorioamnion/skin or lung, since these organs are also in direct contact with the amniotic fluid. The gastrointestinal tract was isolated from the respiratory tract and the amnion/skin epithelia by fetal surgery in time-mated ewes. Lipopolysaccharide (LPS) or saline (controls) was selectively infused in the gastrointestinal tract, trachea, or amniotic compartment at 2 or 6 days before preterm delivery at 124 days gestation (term 150 days). Gastrointestinal and intratracheal LPS exposure caused distinct inflammatory responses in the fetal gut. Inflammatory responses could be distinguished by the influx of leukocytes (MPO(+), CD3(+), and FoxP3(+) cells), tumor necrosis factor-α, and interferon-γ expression and differential upregulation of mRNA levels for Toll-like receptor 1, 2, 4, and 6. Fetal gut inflammation after direct intestinal LPS exposure resulted in severe loss of the tight junctional protein zonula occludens protein 1 (ZO-1) and increased mitosis of intestinal epithelial cells. Inflammation of the fetal gut after selective LPS instillation in the lungs caused only mild disruption of ZO-1, loss in epithelial cell integrity, and impaired epithelial differentiation. LPS exposure of the amnion/skin epithelia did not result in gut inflammation or morphological, structural, and functional changes. Our results indicate that the detrimental consequences of chorioamnionitis on fetal gut development are the combined result of local gut and lung-mediated inflammatory responses.

Phenotype of entero-endocrine L cells becomes restricted during development.

BACKGROUND: Glucagon-like peptide (GLP)-1 and glucose-dependent insulinotropic polypeptide (GIP) are hormones secreted by L and K cells, respectively, and by LK cells. To characterize L and K cells during development, we examined ileum from embryonic (e)- 12 to e-17. RESULTS: GLP-1 cells were first seen at e-15 and their number increased at e-17. At e-17, most GLP-1 cells co-expressed GIP. The transcription factors Pax6 and Pdx-1 are required for GIP expression, while Pax6 activates the expression of GLP-1. At e-17, the mucosa has GIP+ Pax6+, GIP+ Pdx-1+, GLP-1+ Pax6+, and GLP-1+ Pdx-1+ cells. Unlike ileal L cells of postnatal and adult mice, a subset of ileal L cells of e-17 embryos co-expressed GLP-1 and glucagon (Glu). Glu-positive cells contain proprotein-convertase 2 (PC2) and PC3/1, the enzymes responsible for Glu and GLP-1 synthesis, respectively. CONCLUSIONS: Our findings indicate that most GLP-1+ cells of ileum of e-17 embryos co-express GIP and, therefore, are LK cells. In addition, a subset of GLP-1+ cells of embryos but not of neonates co-express glucagon, indicating that the expression of Glu in GLP-1+ cells disappears after birth.

Mesenteric artery reactivity and small intestine morphology in a chicken model of hypoxia-induced fetal growth restriction.

Infants with intrauterine growth retardation are prone to intestinal disorders. The morphological and molecular mechanisms that lead to these complications are not completely understood and suitable experimental models are necessary. The aim of this study was to characterize mesenteric artery (MA) reactivity, small intestine morphometry and intestinal expression of vascular endothelial growth factor (VEGF) in a chicken model of hypoxia-induced fetal growth restriction. Chicken embryos (15 and 19 incubation days) and hatchlings (<3-h-old and 1-d-old) were incubated under hypoxic (15% O2 from day 0 to day 19 of incubation) or normoxic conditions. Vascular reactivity was studied using wire miography. Intestinal morphometry was assessed in hematoxyline-eosine-stained sections. VEGF mRNA expression was determined by RT-PCR analysis. Hypoxia increased the responsiveness of chicken embryo MAs to the adrenergic agonist norepinephrine, the polypeptide endothelin (ET)-1, and the nitric oxide donor sodium nitroprusside and decreased the responsiveness to the endothelium-dependent relaxant agonist acetylcholine. However, the majority of these alterations, with the exception of the hyperresponsiveness to ET-1, were not present in the hypoxic hatchlings. When intestinal histology was analyzed, subtle hypoxia-induced changes were noted in the villi and the muscularis propria from the hatchlings. Hypoxic incubation also diminished the expression of VEGF mRNA in the terminal ileum of the hatchlings. In conclusion, chronic moderate hypoxia during incubation results in subtle but significant alterations in chicken MA reactivity, small intestine morphology and VEGF expression. Whether these alterations may have a direct effect on the functional status of the intestine remains to be investigated.

Gene-expression profile analysis in the mid-gestation human intestine discloses greater functional immaturity of the colon as compared with the ileum.

BACKGROUND AND OBJECTIVES: The occurrence of many neonatal inflammatory intestinal diseases in preterm infants highlights the susceptibility of the immature intestine to responding inadequately to nutrients and microbes. A better understanding of functional intestinal development is essential for the design of optimal treatments ensuring survival and growth of premature infants. The purpose of this study was to evaluate the gene expression profiles of the human ileum and colon at mid-gestation because these 2 segments are considered to be similar at this stage and are the sites of the most frequent pathologies in preterm infants. SUBJECTS AND METHODS: We compared the gene-expression profiles of human fetal small and large intestines using a cDNA microarray and analyzed the data with Ingenuity Pathway Analysis software. RESULTS: We found that a significant proportion of the genes was differentially expressed in the 2 segments. Gene cluster analysis revealed an even higher level of transcriptional dissimilarity at the functional level. For instance, segment-specific/overexpressed gene clusters in the ileum included genes involved with amino acid, vitamin, and mineral metabolism, reflecting the higher level of maturity of the small intestine as compared with the colon in which genes involved with cell cycle, cell death, and cell signaling were the predominant clusters of genes expressed. CONCLUSIONS: Functional clustering analysis of the differentially expressed genes revealed important functional differences between the 2 segments and a relative immaturity of the colon, suggesting that already at mid-gestation, the 2 intestinal segments should be considered as 2 distinct organs.

IL-1α mediated chorioamnionitis induces depletion of FoxP3+ cells and ileal inflammation in the ovine fetal gut.

BACKGROUND: Endotoxin induced chorioamnionitis increases IL-1 and provokes an inflammatory response in the fetal ileum that interferes with intestinal maturation. In the present study, we tested in an ovine chorioamnionitis model whether IL-1 is a major cytokine driving the inflammatory response in the fetal ileum. METHOD: Sheep bearing singleton fetuses received a single intraamniotic injection of recombinant ovine IL-1α at 7, 3 or 1 d before caesarian delivery at 125 days gestational age (term = 150 days). RESULTS: 3 and 7 d after IL-1α administration, intestinal mRNA levels for IL-4, IL-10, IFN-γ and TNF-α were strongly elevated. Numbers of CD3+ and CD4+ T-lymphocytes and myeloidperoxidase+ cells were increased whereas FoxP3+ T-cells were detected at low frequency. This increased proinflammatory state was associated with ileal mucosal barrier loss as demonstrated by decreased levels of the intestinal fatty acid binding protein and disruption of the tight junctional protein ZO-1. CONCLUSION: Intraamniotic IL-1α causes an acute detrimental inflammatory response in the ileum, suggesting that induction of IL-1 is a critical element in the pathophysiological effects of endotoxin induced chorioamnionitis. A disturbed balance between T-effector and FoxP3+ cells may contribute to this process.

ω-3 fatty acids attenuate mucosal inflammation in premature rat pups.

BACKGROUND: Necrotizing enterocolitis (NEC) is a devastating intestinal disease of premature infants. Although ω-3 fatty acids are known to have antiinflammatory effects, their effect against NEC remains unclear. METHODS: Mother rats fed a soybean-based, docosahexaenoic acid (DHA)- or eicosapentaenoic acid (EPA)-enriched diet from days 7 to 20 of gestation were examined. On day 20, the rat pups were delivered by abdominal incision, their intestines were removed, and messenger RNA was extracted. A rat NEC model was used to confirm the effects of ω-3 fatty acids on the inflamed intestine (n = 20-28). The expression of inflammatory molecules was analyzed by real-time polymerase chain reaction (n = 11-14). RESULTS: The concentrations of DHA and EPA in the intestine were significantly increased in the DHA and EPA groups (P < .01). The expression of the antiinflammatory prostaglandin E2 receptor EP3 was increased in the DHA (P < .05) and EPA groups (P < .01). In the NEC model, the reduced incidence of colitis was confirmed in the DHA and EPA groups. The expression of peroxisome proliferator-activated receptor γ was increased (P < .05), and the inhibitor of nuclear factor-κB α/ß decreased in both the DHA (P < .01) and EPA groups (P < .05). CONCLUSION: Our findings indicate that ω-3 fatty acids are beneficial for protecting the premature intestine from inflammation by regulating eicosanoid- and nuclear factor-κB-related metabolite expression.

Regulation of Dab2 expression in intestinal and renal epithelia by development.

Disabled-2 (Dab2) is an intracellular adaptor protein proposed to function in endocytosis. Here, we investigate the intestinal and renal Dab2 expression versus maturation. Dab2 mRNA levels measured by RT-PCR are greater in the small than in the large intestine. Immunological studies localize Dab2 to the terminal web domain of the enterocytes and reveal the presence of a 96-kDa Dab2 isoform in the apical membrane of the jejunum, ileum, and renal cortex of the suckling and adult rat. A 69-kDa Dab2 isoform is only observed in the apical membranes of the suckling ileum. During the suckling period, the Dab2 mRNA levels measured in the enterocytes and crypts and those of the 96-kDa Dab2 isoform are greater in the ileum than in the jejunum. No segmental differences are observed in the adult intestine. In the intestine, the levels of Dab2 mRNA and those of the 96-kDa Dab2 isoform decrease to adult values at weaning, whereas in the kidney they increase with development. Weaning the pups on a commercial milk diet slows the periweaning decline in the levels of Dab2 mRNA in the crypts and of those of the 96-kDa isoform. This is the first report showing that the 96-kDa Dab2 isoform is expressed at the apical domain of rat small intestine, that ontogeny regulates Dab2 gene expression in intestine and kidney and that retarding weaning affects intestinal Dab2 gene expression.

Pathogenic implications of remnant vitelline structures in gastroschisis.

PURPOSE: The pathogenesis of gastroschisis is unknown. It may be helpful in understanding its pathogenesis to know the structural relationships among umbilical components including umbilical vessels, urachus, and vitelline structures, and thus, the authors investigated the remnants of vitelline structures in a series of cases of gastroschisis. METHODS: Medical records of 41 cases with gastroschisis treated in our institute from 1979 to 2009 were retrospectively reviewed. RESULTS: Paraumbilical bands, possible remnants of vitelline structures, were observed in 4 cases (9.8%). All 4 bands were attached to the skin edge of the abdominal defect without incorporation into the umbilical cord. The band ended at the mesentery in 3 cases and at the antimesenteric site of the ileum in the remaining case. Histologic findings showed fibrous tissues in all cases. One was possibly associated with the development of colonic atresia. Another was noticed after silo reduction when herniated bowels became strangulated by the band. The other 2 cases were uncomplicated. CONCLUSIONS: Our findings may support the recently proposed hypothesis that the developmental failure of the yolk sac and related vitelline structures to merge with or to be incorporated into the umbilical stalk might be associated with the pathogenesis of the abdominal wall defect in gastroschisis. Paraumbilical bands derived from vitelline structures may possibly cause intestinal ischemia prenatally or postnatally.