Decidual cells and decidualization in the carnivoran endotheliochorial placenta

Decidualization is considered a distinctive feature of eutherian pregnancy, and has appeared during evolution along with the development of invasive forms of placentation, as the endotheliochorial placenta. Although decidualization is not massive in carnivores, as it is in most species developing hemochorial placentas, isolated or grouped cells regarded as decidual have been documented and characterized, mainly in bitches and queens. For the majority of the remaining species of the order, data in the bibliography are fragmentary. In this article, general morphological aspects of decidual stromal cells (DSCs), their time of appearance and lasting, data about the expression of cytoskeletal proteins and molecules considered as markers of decidualization were reviewed. From the data reviewed, it follows that carnivoran DSCs take part either in the secretion of progesterone, prostaglandins, relaxin, among other substances, or at least in the signaling pathways triggered by them. Beyond their physiological roles, some of those molecules are already being used, or are yet under study, for the non-invasive endocrine monitoring and reproductive control of domestic and wild carnivores. Only insulin-like growth factor binding protein 1, among the main decidual markers, has been undoubtedly demonstrated in both species. Laminin, on the contrary, was found only in feline DSCs, and prolactin was preliminary reported in dogs and cats. Prolactin receptor, on the other hand, was found in both species. While canine DSCs are the only placental cell type expressing the nuclear progesterone receptor (PGR), that receptor has not been demonstrated neither in feline DSCs, nor in any other cell in the queen placenta, although the use of PGR blockers leads to abortion. Against this background, and from the data gathered so far, it is unquestionable that DSCs in carnivorans do play a pivotal role in placental development and health. The knowledge about placental physiology is critical for medical care and breeding management, primarily in domestic carnivores; it is also absolutely crucial for a conservation approach in the management of endangered carnivore species.Fil: Diessler, Mónica Elizabeth. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC);Fil: Hernández, Rocío. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC); . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Gomez Castro, María Gimena. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC); . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Barbeito, Claudio Gustavo. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada (LHYEDEC); . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Altered E-cadherin/β-catenin expression in feline cutaneous squamous cell carcinomas

Cutaneous squamous cell carcinoma (CSCC) is the most common malignant skin tumour in cats and the nature of the molecular mechanisms involved is poorly defined. Included among the molecular mechanisms in human and canine CSCCs is altered expression of E-cadherin/β-catenin. This study aimed to explore the immunohistochemical expression pattern of E-cadherin and β-catenin in 43 samples of feline CSCC by using a tissue microarray to elucidate whether expression of these molecules is dysregulated. Membrane expression of E-cadherin and membrane and cytoplasmic expression of β-catenin were significantly reduced in the CSCCs. Cytoplasmic expression of E-cadherin and nuclear expression of β-catenin were also found in some CSCCs. These findings indicate that altered expression of E-cadherin and β-catenin is a frequent event in feline CSCCs, suggesting that these molecules play an important role in acquisition of the malignant phenotype in feline patients with CSCC. The results also suggest the existence of a subpopulation of feline patients with CSCC in which the Wnt pathway may contribute to epidermal carcinogenesis.Fil: Sanz Ressel, Berenice Liyare. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Gomez Castro, María Gimena. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Massone, Adriana Raquel. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Patología. Laboratorio de Patología Especial Veterinaria "Dr. Bernardo Epstein"; ArgentinaFil: Barbeito, Claudio Gustavo. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentin

Comparative matrix metalloproteinase-2 and -9 expression and activity during endotheliochorial and hemochorial trophoblastic invasiveness

To establish a functional placenta, its development needs adequate trophoblastic invasiveness. The intricate and complex morphological and molecular aspects regulating trophoblastic invasion during endotheliochorial placentation of domestic carnivores and their similarities and differences with the hemochorial placenta are still poorly understood. During placentation processes, from the time of implantation, trophoblast cells invade the uterine endometrium where they achieve extensive degradation and remodeling of extracellular matrix components; in this process, matrix metalloproteinases (MMPs), particularly MMP-2 and 9, have an essential role in rebuilding, cell migration, and invasiveness. This review provides an overview of comparative trophoblast invasive events and the expression and activity of MMP-2 and 9 during endotheliochorial and hemochorial placentation, emphasizing dog and mouse placental models. Understanding of trophoblastic invasiveness in two models of placentation, the intermediately invasive domestic carnivore endotheliochorial placenta, and the more highly invasive mouse hemochorial placenta, contributes to deepen knowledge of the trophoblast invasive processes and their diverse and complex human placental alterations, such as preeclampsia.Fil: Gualdoni, Gisela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; ArgentinaFil: Gomez Castro, María Gimena. Universidad Nacional del Nordeste. Facultad de Cs.veterinarias. Departamento de Cs.basicas. Cátedra de Histología y Embriologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Hernández, Rocío. Universidad Nacional del Nordeste. Facultad de Cs.veterinarias. Departamento de Cs.basicas. Cátedra de Histología y Embriologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Barbeito, Claudio Gustavo. Universidad Nacional del Nordeste. Facultad de Cs.veterinarias. Departamento de Cs.basicas. Cátedra de Histología y Embriologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Cebral, Elisa. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Biodiversidad y Biología Experimental y Aplicada. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Biodiversidad y Biología Experimental y Aplicada; Argentin

Characterising the expression of the organic cation transporter OCT3 in cutaneous papillomas of dogs

Background: The identification of the activation of the mammalian targetof rapamycin (mTOR) signalling pathway as a frequent molecular event incanine cutaneous papillomas (CPs) has provided the rational foundation toexplore novel molecular-targeted therapies. Recent evidence indicates thatmetformin reduces the size of CPs in mice by inhibiting the mTOR signallingpathway. These effects require the expression of the organic cation transporter 3 (OCT3/SLC22A3), a well-known metformin uptake transporter.Hypothesis/Objectives: The aim of the present study was to characterisethe expression pattern of the metformin uptake transporter OCT3 in caninesamples of CP that have shown activation of the mTOR signalling pathwayin order to predict if this hyperplastic epidermal lesion is potentially sensitiveto metformin.Methods: The expression of OCT3 was evaluated by immunohistochemicalinvestigation in sections of a previously constructed tissue microarray containing 28 samples of canine CP and compared with that previously evaluatedfor the mTOR activation marker pS6. Results: OCT3 was highly expressed in the membrane and cytoplasm ofthe basal and suprabasal epidermal cells in all samples of canine CP. ThisOCT3 expression was localised at similar epidermal compartments to thoseobserved for pS6.Conclusions and Clinical Relevance: These results show that canine CPsexhibit the expression of surrogate markers that suggest sensitivity to metformin, such as upregulated OCT3 and pS6 expression. Taken together, thesefindings provide the rationale for the early assessment of the use of metformin as a mechanism-based therapeutic approach for treating canine patients with persistent or multiple CPs.Fil: Sanz Ressel, Berenice Liyare. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Gomez Castro, María Gimena. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada; . Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Mórtola, Eduardo Carlos. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Centro de Microbiología Básica y Aplicada;Fil: Massone, Adriana Raquel. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Patología. Laboratorio de Patología Especial Veterinaria "Dr. Bernardo Epstein"; ArgentinaFil: Barbeito, Claudio Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de la Plata. Facultad de Ciencias Veterinarias. Laboratorio de Histología y Embriología Descriptiva, Experimental y Comparada

Term placenta of the southern elephant seal (Mirounga leonina)

Introduction: The pinnipeds’ placenta has been described as zonary, annular, labyrinthic and endotheliochorial, like that of the terrestrial carnivores. This article describes the placenta of Mirounga leonina, a phocid pinniped, focusing on some morphological features related to fetal nutrition. Methods: Placental samples from three elephant seals were collected and conditioned after natural delivery at the Antarctic Specially Protected Area 132. Histological and ultrastructural studies were conducted; cytokeratins, vimentin, α-smooth muscle actin, and desmin proteins were detected using immunohistochemistry. Results: The placentas were zonary, lobed, belt-shaped, and showed multiple vivid orange areas, which corresponded to bilirubin crystalline pigment found among chorionic villi and inside trophoblast cells. In the labyrinth, cytotrophoblast cells were isolated and there was a scant syncytium interposed between maternal and fetal vessels. Fetal vessels were small, round, and frequently intratrophoblastic, while maternal vessels were large, irregular, sinuous, and thin-walled. Vimentin and actin were detected in some scattered non-vascular cells throughout the labyrinth. Broad areas of degenerated and necrotic maternal components were also observed. Discussion: The placentas of pinniped and fissiped carnivores share several traits. However, some remarkable features might maximize respiratory efficiency, collaborating to endure deep-diving hypoxia. Some of them, as the notably large sinuous maternal capillaries and fetal capillary indentation into the syncytium, are shared, e.g., by Phocidae and Mustelidae. Besides hemotropic nutrition taking place through an extremely narrow barrier, the abundant necrotic material and hematic products might allow substantial endocytosis of detritus even in term placentas, in this species giving birth to precocious offspring.Fil: Diessler, Mónica Elizabeth. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Migliorisi, Ana Lorena. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Gomez Castro, María Gimena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Favaron, Phelipe Oliveira. Universidade de Sao Paulo; BrasilFil: Zanuzzi, Carolina Natalia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Negrete, Javier. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Direcciñon Nacional del Antartico. Instituto Antártico Argentino. Departamento de Biología de Predadores Tope; ArgentinaFil: Miglino, María Angélica. Universidade de Sao Paulo; BrasilFil: Barbeito, Claudio Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Corrigendum to “Serum progesterone concentration, volume, and apoptosis of corpora lutea in early, middle and late diestrus in the bitch” [Anim. Reprod. Sci. (2020) 106591]

The aim was to study number, volume, apoptosis of corpora lutea (CL), and serum P4 concentrations in early, middle, and late diestrus of dogs. Thirty-six bitches were ovari-hysterectomized (OVX): Early Diestrus (Group [G]1; OVX 20 days after end of estrus [DEH]); Mid-diestrus (GII; OVX between 21 and 40 days after DEH), and Late-diestrus (GIII; OVX between 41 and 60 days after DEH). Before OVX a blood sample was collected to quantify P4. After OVX, the number of CL (NCL) was recorded, CL measured using both ultrasonography (US) and caliper (CAL), and the volume (mm3) was calculated. Based on abundances of caspase-3, apoptotic luteal cells were detected. Bitches in early-diestrus had greater P4 concentrations than bitches in mid- and late- diestrus (23.52 ±3.78 and 10.86 ±3.88 ng/mL; P 0.30). Bitches with CL (≥5) had twice the serum P4 concentrations as bitches with CL1− 2 and CL3− 4 (22.71 ±3.70 and 10.97 ±4.06 ng/mL; P <0.05). There were correlations between P4 concentrations with USCLV, CALCLV, and NCL (r =0.64, r =0.67, r =0.44; P <0.0001). When serum P4 concentrations were adjusted for stages of diestrus, however, there were only correlations during early diestrus. The percentage of apoptotic cells was greater in GIII compared with GI and GII (13.75 ±2.26 % compared with 4.5 ±0.68 % and 4.6 ±1.5 %, respectively; P <0.05). As days of diestrus increased, number of apoptotic cells increased, and serum P4 concentrations decreased.Fil: Stornelli, María Cecilia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: Praderio, Romina Gisele. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Clínica. Cátedra de Reproducción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: García, María Florencia. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias. Departamento de Clínica. Cátedra de Reproducción Animal; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Nuñez Favre, Romina de Los Angeles. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; ArgentinaFil: García Mitacek, María Carla. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Gomez Castro, María Gimena. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: de la Sota, Rodolfo Luzbel. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; ArgentinaFil: Stornelli, María Alejandra. Universidad Nacional de La Plata. Facultad de Ciencias Veterinarias; Argentin

Does the Use of Immunosuppressive Drugs Impact on SARS-CoV-2 Infection Outcome? Data From A National Cohort of Patients With Immune-Mediated Inflammatory Diseases (SAR-COVID Registry)

Background/objectiveThis study describes the impact of immunomodulatory and/or immunosuppressive (IM/IS) drugs in the outcomes of COVID-19 infection in a cohort of patients with immune-mediated inflammatory diseases (IMIDs).MethodsAdult patients with IMIDs with a confirmed SARS-CoV-2 infection were included. Data were reported by the treating physician between August 13, 2020 and July 31, 2021. Sociodemographic data, comorbidities, and DMARDs, as well as clinical characteristics, complications, and treatment of the SARS-CoV-2 infection, were recorded. Descriptive analysis and multivariable logistic regression models were carried out.ResultsA total of 1672 patients with IMIDs were included, of whom 1402 were treated with IM/IS drugs. The most frequent diseases were rheumatoid arthritis (47.7%) and systemic lupus erythematosus (18.4%). COVID-19 symptoms were present in 95.2% of the patients. A total of 461 (27.6%) patients were hospitalized, 8.2% were admitted to the intensive care unit, and 4.4% died due to COVID-19.Patients without IM/IS treatment used glucocorticoids less frequently but at higher doses, had higher levels of disease activity, were significantly older, were more frequently hospitalized, admitted to the intensive care unit, and died due to COVID-19. After adjusting for these factors, treatment with IM/IS drugs was not associated with a worse COVID-19 outcome (World Health Organization-Ordinal Scale ≥5) (odds ratio, 1.24; 95% confidence interval, 0.73-2.06).ConclusionsSAR-COVID is the first multicenter Argentine registry collecting data from patients with rheumatic diseases and SARS-CoV-2 infection. After adjusting for relevant covariates, treatment with IM/IS drugs was not associated with severe COVID-19 in patients with IMIDs.Study registrationThis study has been registered in ClinicalTrials.gov under the number NCT04568421

Environmental and societal factors associated with COVID-19-related death in people with rheumatic disease: an observational study

Published by Elsevier Ltd.Background: Differences in the distribution of individual-level clinical risk factors across regions do not fully explain the observed global disparities in COVID-19 outcomes. We aimed to investigate the associations between environmental and societal factors and country-level variations in mortality attributed to COVID-19 among people with rheumatic disease globally. Methods: In this observational study, we derived individual-level data on adults (aged 18-99 years) with rheumatic disease and a confirmed status of their highest COVID-19 severity level from the COVID-19 Global Rheumatology Alliance (GRA) registry, collected between March 12, 2020, and Aug 27, 2021. Environmental and societal factors were obtained from publicly available sources. The primary endpoint was mortality attributed to COVID-19. We used a multivariable logistic regression to evaluate independent associations between environmental and societal factors and death, after controlling for individual-level risk factors. We used a series of nested mixed-effects models to establish whether environmental and societal factors sufficiently explained country-level variations in death. Findings: 14 044 patients from 23 countries were included in the analyses. 10 178 (72·5%) individuals were female and 3866 (27·5%) were male, with a mean age of 54·4 years (SD 15·6). Air pollution (odds ratio 1·10 per 10 μg/m3 [95% CI 1·01-1·17]; p=0·0105), proportion of the population aged 65 years or older (1·19 per 1% increase [1·10-1·30]; p<0·0001), and population mobility (1·03 per 1% increase in number of visits to grocery and pharmacy stores [1·02-1·05]; p<0·0001 and 1·02 per 1% increase in number of visits to workplaces [1·00-1·03]; p=0·032) were independently associated with higher odds of mortality. Number of hospital beds (0·94 per 1-unit increase per 1000 people [0·88-1·00]; p=0·046), human development index (0·65 per 0·1-unit increase [0·44-0·96]; p=0·032), government response stringency (0·83 per 10-unit increase in containment index [0·74-0·93]; p=0·0018), as well as follow-up time (0·78 per month [0·69-0·88]; p<0·0001) were independently associated with lower odds of mortality. These factors sufficiently explained country-level variations in death attributable to COVID-19 (intraclass correlation coefficient 1·2% [0·1-9·5]; p=0·14). Interpretation: Our findings highlight the importance of environmental and societal factors as potential explanations of the observed regional disparities in COVID-19 outcomes among people with rheumatic disease and lay foundation for a new research agenda to address these disparities.MAG is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K01 AR070585 and K24 AR074534 [JY]). KDW is supported by the Department of Veterans Affairs and the Rheumatology Research Foundation Scientist Development award. JAS is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (grant numbers K23 AR069688, R03 AR075886, L30 AR066953, P30 AR070253, and P30 AR072577), the Rheumatology Research Foundation (K Supplement Award and R Bridge Award), the Brigham Research Institute, and the R. Bruce and Joan M. Mickey Research Scholar Fund. NJP is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (T32-AR-007258). AD-G is supported by grants from the Centers for Disease Control and Prevention and the Rheumatology Research Foundation. RH was supported by the Justus-Liebig University Giessen Clinician Scientist Program in Biomedical Research to work on this registry. JY is supported by grants from the National Institutes of Health (K24 AR074534 and P30 AR070155).info:eu-repo/semantics/publishedVersio