Deregulated ephrin-B2 expression in the mammary gland interferes with the development of both the glandular epithelium and vasculature and promotes metastasis formation

Eph receptor tyrosine kinases and their membrane-bound ephrin ligands play key roles during morphogenesis and adult tissue homeostasis. Receptor-ligand interactions result in forward and reverse signalling from the receptor and ligand respectively. To delineate the role(s) of forward and reverse signalling in mammary gland biology we have established transgenic mice exhibiting mammary epithelial-specific overexpression of either the native ephrin-B2 or a dominant negative ephrin-B2 mutant incapable of reverse signalling. During pregnancy and lactation overexpression of the native ephrin-B2 resulted in precocious differentiation, whereas overexpression of mutated ephrin-B2 caused delayed epithelial differentiation and in disturbed tissue architecture. Both transgenes affected also mammary vascularisation. Whereas ephrin-B2 induced superfluous but organised capillaries, mutant ephrin-B2 overexpression resulted in an irregular vasculature with blind-ending capillaries. Mammary tumours were not observed in either transgenic line, however, the crossing with NeuT transgenic animals revealed that mutated ephrin-B2 expression significantly accelerated tumour growth and imposed a metastatic phenotype.

Ultrastructural features of the glandular region of the stomach of Piaractus mesopotamicus (Holmberg, 1887) with emphasis on the oxyntopeptic cell

The characteristics of the lining and glandular epithelial types of the wall of the stomach of pacu (Piaractus mesopotamicus Holmberg, 1887) were studied by transmission electron microscopy. Columnar mucous cells were observed in the lining epithelial surface and the glandular epithelium that invaginated in the lamina propria showed secretory cells or oxyntopeptic cells as called by some authors in the literature. The columnar epithelial cells are narrow and show a basal nucleus. They are rich in organelles and contain secretory granules of round or rectangular shape heterogeneously electron dense in the apical portion. In the basal region of the glands there are secretory cells. The luminal half of these cells has abundant tubules (tubulo-vesicular system) that communicate with the external medium. Deeper basally in the cytoplasm there are the nucleus, mitochondria of various shapes and other scattered organelles.

Timely topic: Premalignant lesions associated with adenocarcinoma of the upper gastrointestinal tract

The changing incidence of adenocarcinomas, particularly in the oesophagus and gastric cardia, has led to the rapid expansion of screening programmes aimed at detecting the precursor lesion of dysplasia before adenocarcinoma develops. The pathologist now has an important role in first diagnosing patients at risk for developing dysplasia, and then correctly classifying dysplasia when it occurs. Barrett's oesophagus has had different diagnostic criteria in previous years but is currently diagnosed by the presence of intestinal metaplasia of any length in the true oesophagus. Intestinal metaplasia confined only to the gastro-oesophageal junction or cardia is of uncertain significance but is probably common, with less risk of progressing to dysplasia or malignancy. In the stomach, patients with autoimmune atrophic gastritis and Helicobacter-associated multifocal atrophic gastritis have an increased risk of adenocarcinoma, but screening protocols are not well-developed compared with those used for Barrett's oesophagus. Dysplasia of glandular epithelium can be classified using well-described criteria. Low grade dysplasia is the most common type and regresses or remains stable in the majority of patients. High grade dysplasia is more ominous clinically, with a propensity to coexist with or progress to adenocarcinoma.

Effects of age on histological parameters of the sweat glands of Nellore cattle

The sweat glands are important in thermoregulation of cattle in a warm environment as they help dissipate heat through evaporation. Studies on gland histology are important to define its secretion potential and the capacity of perspiration and heat removal. The objective of this study was to determine, by histomorphometry, glandular epithelium height, the depth of the gland, length of the glandular portion and number of glands per cm2 of the sweat glands of the three age groups of Nellore cattle. Thirty females were used in this study. They were equally divided into calves, heifers and cows. Histological sections were obtained and analyzed by digital images in Trinocular BX40 Olympus microscope coupled to an Oly - 200 camera, connected to a computer. The images were obtained with microscope with 2x, 4x, 10x and 40x magnification objectives. The measurements were performed using HL Image 97 program. The height of glandular epithelium, depth of the glands, length and density of the glandular portion per cm2 , were all analyzed. The calves showed greater height of the glandular epithelium than heifers (P = 0.0024), and cows (P = 0.0191). The depth of the gland was not influenced by age. Cows had higher length of secretory portion than heifers (P = 0.0379) and calves (P = 0.0077). Heifers had a greater number of sweat glands per cm2 of skin than cows (P = 0.023). In cattle, the height of glandular epithelium and the density decreases as animals get older. On the other hand, the length of the secretor portion increases but with no changes in the depth of the sweat glands

The materno-fetal interface in llama (Lama guanicoe glama)

Samples from 9 llamas (28 through 36 weeks of gestation) were collected and fixed in 4% buffered paraformaldehyde (light microscopy) and in 2.5% buffered glutaraldehyde (transmission and scanning electron microscopy). The material was processed in paraplast and slides (5mm) were stained with HE, PAS, Masson-Trichrome, acid phosphatase and Perl's. The uteroferrin was immunolocalized. The results show that llama placenta is chorioallantoic, diffuse, folded and epitheliochorial, and the fetus is covered with an epidermal membrane. The trophoblast cells have variable morphology: cubic, rounded and triangular cells, with cytoplasm containing PAS-positive granules. Binucleated cells with large cytoplasm and rounded nuclei, as well as giant trophoblastic cells with multiple nuclei were also observed. Numerous blood vessels were observed beneath the cells of the uterine epithelium and around the chorionic subdivided branches. Glandular activity was shown by PAS, Perl's, and acid phosphatase positive reactions in the cytoplasm and glandular lumen, and by immunolocalization of the uteroferrin in the glandular epithelium. The uterine glands open in spaces formed by the areoles, which are filled by PAS-positive material. The llama fetus was covered by the epidermal membrane, composed of stratified epithelium, with up to seven layers of mono-, bi- or trinucleated cells. The high level of maternal and fetal vascularization surfaces indicates an intense exchange of substances across both surfaces. The metabolic activity shown in the uterine glands suggests an adaptation of the gestation to the high altitudes of the natural habitat of this species.

Morphological and morphometric evaluation of prepubertal gilt ovaries, uterine tubes and uterus at different oestrus cycle stages

Studies are performed in developing techniques/procedures that provide greater reproductive performance in farm animals, including pigs. In this sense, the study of gilts reproductive organs at different oestrus cycle stages for assessing the presence of abnormalities and/or other parameters that may affect the future animal fertility is important. In order to evaluate the morphological, morphometric and histomorphometric features of ovaries, uterus and uterine tubes (UTs) characteristics of prepubertal gilts at different oestrus cycle stages, reproductive tracts from 48 animals immediately after slaughter were obtained. After, the structures were dissected and removed, and the ovaries were used for classification of oestrus cycle stage of each gilt in follicular phase (FP) and luteal phase (FL). Then, morphometric evaluations of ovaries, UTs, uterine horns and uterine body were performed. Besides that, medial segments of UTs and uterus were fixed in Bouin solution, processed and included in paraffin, when histological sections of 5.0 micrometers (µm) were obtained and stained with Hematoxylin and Eosin. Histomorphometric analyzes using image capture system and specific software were performed. Afterwards, data were submitted to Student's t test for assessment the statistical differences (P<0.05) between the two different oestrus cycle stages (FP × LP) and between the placement of reproductive structures (right × left antimer). Among the gilts evaluated, 35 were in the FP and 13 in LP. There was no difference (P>0.05) between morphometric parameters of ovaries, UTs and uterus of gilts in FP and LP. Likewise, in respect to the placement of reproductive structures, both in the oestrus cycle stages, as in the general average, there was no difference (P>0.05). Regarding the histomorphometric variables, gilts classified in FP presented a higher (P<0.05) height of glandular and UT epithelium compared to animals in LP. On the other hand, the diameter of endometrial glands was higher (P<0.05) in gilts at LP compared to FP. Furthermore, gilts in LP presented a higher (P<0.05) proportion of endometrium occupied by glands, whereas animals in FP had a higher (P<0.05) proportion of connective tissue and blood vessels. In conclusion, in prepubertal gilts, the histomorphometric parameters as endometrial glands diameter, the height of glandular epithelium and of UT epithelium and the proportion of endometrium occupied by connective tissue, besides the glands and blood vessels varies through the oestrus cycle, possibly under the influence of ovarian steroids.

Conceptus-mediated endometrial vascular changes during early pregnancy in mares: an anatomic, histomorphometric, and vascular endothelial growth factor receptor system immunolocalization and gene expression study

This work examined how the conceptus modulates endometrial tissue remodeling and vascular development prior to implantation in mares. A macroscopic uterine examination was completed at day 21 of pregnancy. In situ morphology revealed that the endometrium involved in encroachment is restricted to the dorsal endometrium immediately overlying the yolk sac. The amount of stromal area occupied by blood vessels and the number of endometrial glands were increased during early pregnancy. Endometrial histomorphometry as well as the endometrial mRNA abundance and immunolocalization of VEGF, VEGFR1, VEGFR2, and Ki-67 was completed at days 14 and 21 of pregnancy, at day 10 of the estrous cycle, and during estrus. No obvious differences in VEGF and VEGFR1 protein localization were detected between pregnant and cycling mares but differential staining pattern for VEGFR2 and Ki-67 was observed. VEGFR2 localized to luminal and glandular epithelium of pregnant mares, while luminal epithelium was negative in cycling mares. Ki-67 staining was weak during the luteal phase but exhibited prominent luminal epithelium staining during estrus. In pregnant mares, all endometrial layers were Ki-67 positive. Quantitative RT-PCR revealed a greater abundance of VEGF mRNA during pregnancy. VEGFR2 transcript abundance was greatest in pregnant mares on day 21. This study supports the concept that the conceptus plays an active role in directing vasculogenesis within the uterus and thereby establishing hemotrophic nutrition that supports pregnancy after implantation. Reproduction (2011) 142 593-603

Avaliação histológica da próstata de cães adultos sexualmente intactos

Avaliou-se histologicamente a próstata de 30 cães adultos e idosos sexualmente intactos que apresentavam ou não sintomatologia clínica de doença prostática, e verificou-se a incidência de possíveis alterações da glândula. Dentre as alterações encontradas, a hiperplasia prostática benigna constituiu o diagnóstico mais comum, 85,6% (n=24), seguida por prostatite crônica, 64,3% (n=18), displasia do epitélio glandular, 42,8% (n=12), atrofia do epitélio glandular, 39,3% (n=11), infiltrado inflamatório focal, 25% (n=7), dilatação glandular focal, 21,4% (n=6), prostatite aguda, 7,1% (n=2), metaplasia escamosa, 3,6%, (n=1), metástase de neoplasia sistêmica, 3,6% (n=1) e abscesso prostático, 3,6% (n=1). Como em muitos casos os cães são assintomáticos, ressalta-se a importância da realização rotineira de exames clínicos específicos, como o toque retal e a ultrassonografia, para o diagnóstico precoce e o tratamento das afecções prostáticas.

Lesions (ulcers and/or erosions) and desquamations location in the gastric mucosa from asymptomatic Quarter Horse foals: endoscopic survey

A úlcera gástrica figura como uma importante causa de desconforto abdominal em eqüinos jovens. de acordo com a localização das lesões na mucosa gástrica, a presença ou ausência de sinais clínicos e possíveis complicações resultantes de sua ocorrência, quatro síndromes clínicas são freqüentemente descritas em potros: 1) Úlceras assintomáticas ou silenciosas; 2) Úlceras sintomáticas ou ativas; 3) Úlceras perfuradas; e 4) Obstruções gástrica ou duodenal. Com o objetivo de se verificar a distribuição de lesões gástricas (úlceras e/ou erosões) e descamações do epitélio aglandular no estômago de eqüinos jovens assim como uma possível relação entre as alterações mencionadas (lesão/descamação) sessenta potros da raça Quarto de Milha não-portadores de sinais clínicos compatíveis com úlceras gástricas foram submetidos à gastroscopia. Os potros foram divididos em quatro faixas etárias de 15 animais cada uma, sendo: 1 a 30 dias, 31 a 60 dias, 61 a 90 dias e 91 a 120 dias de idade. As lesões ocorreram em ordem decrescente de freqüência nas regiões aglandular próximo ao margo plicatus ao longo da curvatura maior, aglandular próximo à cárdia ao longo da curvatura menor, fundo glandular e aglandular e antro. As descamações do epitélio aglandular ocorreram de forma similar nas regiões de fundo e margo plicatus. Não houve associação entre a ocorrência de lesões e descamações.

Imunoistoquímica de útero e cérvice de cadelas com diagnóstico de piometra

Analisou-se a piometra de 31 cadelas, de raças e idades variadas, sendo 25 cadelas com piometra de cérvice aberta e seis de cérvice fechada. Após ovariossalpingo-histerectomia, foram coletados fragmentos da cérvice e do útero para a avaliação imunoistoquímica. Foram analisados os receptores de estrógenos α e β, progesterona e colágenos I e III. Foram realizadas imunomarcações em diferentes regiões da cérvice, como o epitélio glandular, o epitélio luminal e o estroma glandular, assim como em diferentes regiões do útero, como o epitélio glandular e o estroma glandular. As imunomarcações de colágenos I e III foram realizadas nas regiões glandular e muscular da cérvice e do útero. Concentrações de receptores de progesterona foram maiores em cadelas com piometra fechada.

Detecção imunoistoquímica de receptores de estrógeno e progesterona no endométrio de vacas Nelore (Bos taurus indicus) durante o anestro pós-parto

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Expressão de MMP-2 e MMP-9 no endométrio de éguas saudáveis e portadoras de endometrite crônica

Avaliaram-se, por método imunoistoquímico, a expressão e distribuição das metaloproteinases (MMP) 2 e 9 em amostras de endométrio hígido e de éguas portadoras de endometrite crônica. Foram utilizadas 60 biópsias endometriais. A MMP-2 foi observada na parede vascular, nas células estromais e no epitélio glandular, e a imunorreatividade mais intensa foi obtida nas células do epitélio glandular nas endometrites da categoria III e na parede vascular nos endométrios da categoria I. A marcação imunoistoquímica para MMP-9 mostrou-se difusa pelo endométrio e foi observada no epitélio luminal e glandular, na região da parede vascular, nas células estromais, endoteliais e do infiltrado inflamatório. Houve diminuição da marcação imunoistoquímica na região da parede vascular conforme aumentou o grau das lesões endometriais concomitante à diminuição da intensidade da reação. Não houve relação na expressão imunoistoquímica das metaloproteinases estudadas com o tipo de endometrite

Immunohistochemical detection of receptors for oestrogen and progesterone in endometrial glands and stroma during the oestrous cycle in Nelore (Bos taurus indicus) cows

The aim of the present study was to monitor endometrial distribution and concentrations of oestrogen receptors alpha (ER alpha) and progesterone receptors (PR) by immunohistochemistry in Nelore cows (Bos taurus indicus) during the oestrous cycle. Blood samples were collected for progesterone measurement and endometrial samples were taken from the uterine horn contra lateral to the corpus luteum in 16 cows at days 0 (ovulation), 5, 9, 13 and 19 of the oestrous cycle. Immunostaining evaluation for ER alpha and PR in the glandular epithelium and uterine stroma was performed by two methods: positive nuclei counting and staining intensity of the nuclei. Specific positive staining reactions for both receptors were limited to cell nuclei and they were not identified in the cytoplasm. The proportion of ER alpha positive nuclei had a temporal variation throughout the oestrous cycle in both cell types evaluated and was higher in uterine stroma than the glandular epithelium (p < 0.05). The greatest proportion of ER alpha stained nuclei was observed at oestrus and during the initial and mid luteal phase (days 5, 9 and 13) (p < 0.05) in the glandular epithelium and at days 0, 5 and 9 in the uterine stroma (p < 0.01). The proportion of PR positive nuclei remained constant throughout the entire oestrous cycle for both cell types evaluated (p > 0.05). A higher proportion of PR positive nuclei was measured in the uterine stroma compared with the glandular epithelium (p < 0.05). Intensity of staining for ER alpha and PR varied throughout the oestrous cycle (p < 0.01). There was a higher staining intensity at days 0 and 5 in the stroma for ER alpha (p < 0.01) and PR (p < 0.01) and in the glandular epithelium at days 0, 5, 9 and 13 for ER alpha (p < 0.01) and at days 0, 5 and 9 for PR (p < 0.01) when compared with the other evaluated days. These data demonstrate that ER alpha and PR expression varied throughout the oestrous cycle in Nelore cows, in general with highest concentrations at oestrus and the lowest during the luteal phase. This is similar to patterns observed in Bos taurus taurus.

Histologia e morfometria em cornos uterinos de cadelas nulíparas, multíparas e tratadas com contraceptivos

Dados histológicos e morfométricos foram obtidos de útero de cadelas nulíparas (n=6), multíparas (n=6) e de cadelas tratadas com contraceptivo (n=6). Para esse fim foram usadas seis amostras de cornos uterinos, em corte médio, para cada grupo. As mensurações das espessuras da parede uterina, endométrio total, miométrio total, miométrio interno, miométrio externo, estrato vascular e diâmetro das glândulas endometriais normais não foram estatisticamente significantes entre as cadelas multíparas e tratadas, com exceção para a altura do epitélio de glândulas normais. As mensurações das espessuras da parede uterina, endométrio total, miométrio total, miométrio interno, diâmetro das glândulas normais e altura do epitélio glandular foram significantes, comparando cadelas nulíparas com as multíparas e/ou tratadas, com exceção para as espessuras do miométrio externo e estrato vascular. Diante dos resultados obtidos, pode-se concluir que os dados numéricos confirmam que (1) o uso de anticoncepcionais e sucessivas gestações afetam a estrutura uterina em seu total; (2) o miométrio externo e estrato vascular foram as regiões que menos sofreram alterações comparando-se os 3 grupos; (3) as variações morfológicas ocorreram com a mesma intensidade no endométrio e miométrio totais para as cadelas tratadas e multíparas, e (4) a presença de glândulas endometriais dilatadas foi o diferencial encontrado nas cadelas tratadas, pois as mesmas estavam ausentes nas multíparas e nulíparas.

Evaluation of the ethanol intake on the Calomys callosus seminal vesicle structure

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)