Abnormal Villi Research Articles

The Interaction of Gut Microbiota Composition and Dietary Starch Form on Gut Health in Aged Mice

Abstract Objectives A high glycemic diet has been shown to increase gut permeability, which is associated with increased disease risk. Our objective was to evaluate the role of gut microbiota in mediating the relationship between dietary starch composition and gut health. Methods A high (HG) or low glycemic (LG) diet was fed in equal amounts to male mice from 12 to 24 months of age. The diets differed only by starch composition, which was 100% rapidly-digested amylopectin in the HG diet or 30% amylopectin/70% amylose in the LG diet. Within each diet, mice were assigned to one of three treatment conditions: continuous broad-spectrum antibiotic treatment (ampicillin and neomycin; HGabx or LGabx), weekly fecal microbiota transplants (FMT) from donor control mice fed the alternate diet (HG[tLG] or LG[tHG]), or a control group receiving no additional treatment. Feces were collected for microbiome analysis. Colon sections were collected for histology. Results The diet affected gut microbiota composition, with significantly greater abundance of Clostridium, Ruminococcus, and Coprobacillus in the HG-fed control animals compared with LG-fed controls. Antibiotic treatment in HG-fed animals resulted in elimination of Bacteroidetes and most Firmicutes and a proliferation of Proteobacteria, whereas LG-fed animals were able to maintain Bacteroidetes and a lower abundance of Proteobacteria. Fecal microbiota transplants altered the gut microbiome and recipients differed from their donors. Histological evaluation of colons showed increased intestinal disease in HG-fed animals across all treatments, including increased inflammatory cell infiltration and abnormal villi. Antibiotic treatment in HG-fed animals resulted in the most severe disease phenotype, and most animals died within 4–6 months on treatment and presented with an enlarged and hemorrhagic cecum upon necropsy. Conclusions The high glycemic diet altered the gut microbiome and increased the prevalence of pathological intestinal morphology, which was further exacerbated with antibiotic treatment. Our work suggests that dietary starch form has a substantial effect on the gut health outcomes, particularly in the context of antibiotic treatment or fecal microbiota transplants. Funding Sources BrightFocus Foundation, USDA/NIFA AFRI, USDA, Stanley N. Gershoff Scholarship, NIH RO1, Thome Memorial Foundation.

Role of ACE I/D polymorphism in pathological assessment of preeclampsia in Pakistan.

BackgroundPreeclampsia (PE) is a pregnancy‐related hypertensive disorder, which may stem from impair placentation. Renin‐angiotensin system is one of the mediators of decidualization and trophoblastic proliferation. In the present study women with PE were studied in a comparison of normotensive controls to determine whether Angiotensin‐converting enzyme (ACE) gene I/D polymorphism affect the placental villi and umbilical cord formation with the assessment of biochemical and clinical risk factors.MethodsTotal 400 blood (PE/controls = 200), 400 urine (PE/controls = 200), 90 tissue samples of UC (PE = 50, controls = 40) and 90 placental tissue samples (PE = 50, controls = 40) were recruited. Histomorphological and Histomorphometric analysis were done for placental and umbilical cord tissues. Blood and serum parameters were analyzed, samples were genotyped for I/D polymorphism. Data were statistically analyzed by Independent sample t‐test, Chi‐square test and the odds ratio.ResultsHistological study revealed significant increase (p < 0.001) in distance from Wharton jelly (in both artery and vein) and outer layer thickness of vein; significant reduction (p < 0.01 and p < 0.05) in the lumen area of artery and vein. Abnormal villi, more syncytial knots (SK) and a significant decrease in elongated and large villi in PE placentas. Analysis of ACE gene determined that genotypic frequencies were statistically significant (p < 0.02) among both groups and DD genotype was predominant in the PE group.ConclusionPresent study reveals that ACE I/D polymorphism might affect the normal placental villi and umbilical cord formation in women with PE. In addition, histological studies and genetic evaluation can provide useful information in the determination of various reasons and mechanisms involved in the pathogenesis of PE in Pakistan.

"Bunch of grapes" in complete hydatidiform mole.

Complete hydatidiform mole is a common cause of gestational bleeding of the first trimester, commonly assessed by ultrasound. It represents an abnormal proliferation of trophoblastic tissue, with no fetal formation, just hydropic villi. These abnormal villi seen in ultrasound are compared to a "bunch of grapes," a classic description of this disease.

Prenatal imaging and pathology of placental mesenchymal dysplasia: a report of three cases

AbstractObjective:Placental mesenchymal dysplasia (PMD) is a rare vascular anomaly characterized by mesenchymal stem villous hyperplasia. Accurate differential diagnosis of PMD is crucial to predict fetal outcomes associated with serious obstetrical complications.Methods:We reviewed the clinical and pathological features and immunohistochemical and imaging findings of three patients with PMD.Results:First trimester sonographic cystic findings identified molar pregnancy or PMD. However, PMD was highly suspected according to the maternal serum human chorionic gonadotropin (hCG) titers, fetal karyotypes, and imaging findings. The outcome of patient 1, in whom placental multicystic areas decreased as pregnancy progressed, was a live birth. In contrast, the babies of patients 2 and 3 were stillborn, and multicystic formations detected during the first trimester completely and consistently occupied the placentas. Pathological and immunohistochemical analyses using anti-CD34 and anti-D2-40 antibodies distinguished the cisternae from multiple small vessels in the villi. Immunohistochemical analyses using anti-CK7 and anti-Ki-67 antibodies did not detect excessive proliferation of trophoblasts. Most abnormal villi associated with PMD comprised stromal cells that did not react with an anti-p57kip2antibody.Conclusion:In patients with PMD, if the percentage of the normal placental area decreases as pregnancy progresses, the possibility of fetal growth restriction and intrauterine fetal demise should always be considered. The immunostaining pattern of CD34 and D2-40 may represent a unique feature of PMD and can provide supporting evidence for the differential diagnosis of PMD.

A case report of placental mesenchymal dysplasia with an increased VEGF-D expression

The pathogenesis of placental mesenchymal dysplasia (PMD) remains unclear. This report presents a case of PMD with a female fetus complicated with intrauterine growth restriction (IUGR). The ultrasound findings were similar to molar pregnancies, but PMD was suspected based on the presence of low β-hCG levels and a normal karyotype. After delivery, pathological examination of the placenta showed dilated villi and thick-walled vessels lacking trophoblast proliferation, which thus led to a diagnosis of PMD. The VEGF-D (Xp22.31) mRNA expression was found to have increased in the abnormal villi. Whether this is an incidental or X-linked gene specific event in, IUGR complicated, PMD pathogenesis warrants further investigation of VEGF-D expression in PMD.

Placental Mesenchymal Dysplasia Is Associated With High Rates of Intrauterine Growth Restriction and Fetal Demise: A Report of 11 New Cases and a Review of the Literature

Placental mesenchymal dysplasia (PMD) is a rare condition of placentomegaly and abnormal chorionic villi often clinically mistakenly as partial hydatidiform mole. However, it is clinicopathologically distinct with high incidence of intrauterine growth restriction (IUGR) and fetal death. This study presents 11 new PMD cases and provides a meta-analysis of the associated IUGR and fetal death rates. The cases were identified between 1971 and 2005, mostly from consultation files. To our knowledge, 71 PMD cases have previously been reported; 15 of these were associated with Beckwith-Wiedemann syndrome (BWS). With the addition of our new results, among all cases without BWS, 50% had IUGR and 43% had intrauterine fetal demise (IUFD) or neonatal death. Females represented 82% of cases. Thus, PMD is associated with high IUGR and IUFD/neonatal death rates and disproportionally affects females. The cause and pathogenesis are yet unknown. The current understanding and hypotheses involving PMD are discussed.

Lack of a cardiac bulge in human growth disorganized embryos: evidence for cardiac malformation leading to pregnancy failure

Introduction: Cardiac malformations occur in some humans who have chromosome abnormalities or malformation syndromes. Genetic control of heart development has been investigated in animal models, and early pregnancy failure is observed in mice when certain genes are altered. We hypothesize that some Growth Disorganized (GD) human embryos have had a failure of cardiac development. We suggest that cardiovascular abnormalities contributed to the pregnancy failure and spontaneous abortion (SAB).Methods: To test this, we reviewed the Embryo Collection of the Perinatal Pathology Service of Magee-Womens Hospital, comparing 35 externally normal embryos, Carnegie Stages 11-16, to 41 externally abnormal embryos, GD 2 and 3, for external evidence of normal heart formation: the presence of a heart bulge. We also evaluated the gross appearance of placenta] villi, if these were stored with the embryo. A difference in frequency of observations between the two groups was sought by χ2 analysis.Results: Each 35 of the normal embryos had a heart bulge, and all 10 of the embryos with stored villi had grossly normal villi. The GD embryos were significantly different. Only 11 of 41 GD embryos (27%) had a heart bulge (X2 =39.3, p<0.001). Of the 17 GD embryos stored with villous tissue, 8 had abnormal villi (47%, χ2 =4.55, p<0.05). The 8 GD embryos without a heart bulge were significantly more likely to have abnormal villi (7 of 8, 88%) when compared to the 9 GD embryos with a heart bulge (2 of 9, 22%, χ2 = 4.86 p<0.05).Conclusions: GD embryos show evidence of failed cardiovascular development. Significantly fewer GD embryos have a heart bulge, and significantly more have abnormal placental villi compared to the normal embryos. Histologic studies of cardiovascular development in these embryos may be useful in understanding normal human heart formation and abnormal heart formation in some cases of pregnancy failure.

Trisomy 21 placentas: histopathological and immunohistochemical findings using proliferating cell nuclear antigen.

The cause of growth retardation in trisomy 21 and other autosomal trisomies is not known, but may be the result of defective cell proliferation, slowing of the cell cycle, or placental structural abnormalities. Abnormalities of the fetal cell cycle may be reflected in placental growth and can be detected using proliferating cell nuclear antigen (PCNA). Twelve second-trimester and six third-trimester trisomy 21 placentas were examined histopathologically and stained immunohistochemically using antibodies to PCNA. Normal age-matched placentas were used as controls. The second-trimester trisomy 21 placentas all exhibited many large irregular hypovascular villi. The third-trimester trisomy 21 placentas showed two patterns: (i) many large, irregular hypovascular villi, and (ii) relatively normal-appearing villi with only a few abnormal villi and focal hypervascularity. PCNA staining was significantly greater in second-trimester placentas when compared to third-trimester placentas for both trisomy 21 and controls. There was no significant difference in PCNA staining in trisomy 21 placentas when compared to the normal age-matched controls. PCNA staining indicates no significant differences in proliferation between normal and trisomy 21 placentas. Trisomy 21 placentas show villus abnormalities, including hypovascularity.

Early recurrent miscarriage: histology of conception products

The histopathological appearance of conception products from 44 women with recurrent miscarriage was compared with those obtained from 105 women with sporadic miscarriage. Abnormal villi, suggesting fetal chromosomal abnormalities, were found in 62% of women with a recurrent miscarriage and in 58% of those with sporadic miscarriage. This difference is not statistically significant.

Enhancement by tetragastrin of experimental induction of gastric epithelium in the duodenum.

The effects of tetragastrin and truncal vagotomy on the incidence of gastric type epithelium in the duodenum by intraduodenal instillation of 5% NaOH solution were investigated in Wistar rats. Prolonged administration of 1 mg tetragastrin/kg body weight in depot form starting one week after NaOH treatment resulted in a significant increase in gastric acid secretion and the incidence and number of villi with gastric epithelium in the duodenum in experimental week 10. Villi with gastric epithelium were found in five (23%) of 22 rats in control group, whereas abnormal villi were found in 13 (59%) of 22 rats in the tetragastrin treated group (p less than 0.05). The average number of villi with gastric epithelium rose from 0.6 (0.4) per 100 villi in control rats to 2.4 (0.6) per 100 villi in tetragastrin treated rats (p less than 0.01). On histological examination, gastric type epithelium was most often found on stunted or flattened villi, and was always within the boundaries of the area of Brunner's glands. These mucosal changes reverted toward normal with time. In week 35, the incidence of gastric epithelium was significantly less than at week 10 (p less than 0.05). In contrast, no villi with gastric epithelium were found in vagotomised rats in week 10 (p less than 0.05). Vagotomy also caused a significant decrease in gastric acid secretion. These results show that exposure of the duodenal mucosa to high levels of gastric acid enhance the induction of gastric eithelium in the duodenum.

SEMIMACROSCOPIC EXAMINATIONS OF THE SURFACE PATTERN OF SMALL INTESTINAL MUCOSA IN CROHN'S DISEASE

The mucosal surface pattern of surgical specimens from small intestine affected by Crohn's disease are studied using Alcian-green staining of whole mounts. The semimacroscopic appearance of the mucosa is described. Our findings include i.a. malformation and enlargement of villi-often to extreme degree-villi frequently showing small vesicles on their apical region. Polypoid structures were found to be avillous as well as covered by normal or abnormal villi. The semimacroscopic observations are compared with observations from conventional light microscopy. The villus enlargement is in the first stages caused by lymphatic dilatation and later by oedema and inflammation.