RESUMO
The microbiome -defined as the microbiota (bacteria, archaea, lower and higher eukaryotes), their genomes, and the surrounding environmental conditions- has a well-described range of physiological functions. Thus, an imbalance of the microbiota composition -dysbiosis- has been associated with pregnancy complications or adverse fetal outcomes. Although there is controversy about the existence or absence of a microbiome in the placenta and fetus during healthy pregnancy, it is known that gut microbiota can produce bioactive metabolites that can enter the maternal circulation and may be actively or passively transferred through the placenta. Furthermore, the evidence suggests that such metabolites have some effect on the fetus. Since the microbiome can influence the epigenome, and modifications of the epigenome could be responsible for fetal programming, it can be experimentally supported that the maternal microbiome and its metabolites could be involved in fetal programming. The developmental origin of health and disease (DOHaD) approach looks to understand how exposure to environmental factors during periods of high plasticity in the early stages of life (e.g., gestational period) influences the program for disease risk in the progeny. Therefore, according to the DOHaD approach, the influence of maternal microbiota in disease development must be explored. Here, we described some of the diseases of adulthood that could be related to alterations in the maternal microbiota. In summary, this review aims to highlight the influence of maternal microbiota on both fetal development and postnatal life, suggesting that dysbiosis on this microbiota could be related to adulthood morbidity.
Assuntos
Microbioma Gastrointestinal , Microbiota , Gravidez , Feminino , Humanos , Disbiose/microbiologia , Placenta/microbiologia , Desenvolvimento FetalRESUMO
Antiphospholipid syndrome is an autoimmune disease characterized by the persistent presence of antiphospholipid antibodies, along with occurrence of vascular thrombosis and pregnancy morbidity. The variety of antiphospholipid antibodies and their related mechanisms, as well as the behavior of disease in wide groups of patients, have led some authors to propose a differentiation of this syndrome into two independent entities: vascular and obstetric antiphospholipid syndrome. Thus, previous studies have discussed whether specific autoantibodies may be responsible for this differentiation or, in contrast, how the same antibodies are able to generate two different clinical presentations. This discussion is yet to be settled. The capability of serum IgG from patients with vascular thrombosis to trigger the biogenesis of endothelial cell-derived microparticles in vitro is one of the previously discussed differences between the clinical entities of antiphospholipid syndrome. These vesicles constitute a prothrombotic mechanism as they can directly lead to clot activation in murine models and recalcified human plasma. Nevertheless, other indirect mechanisms by which microparticles can spread a procoagulant phenotype could be critical to understanding their role in antiphospholipid syndrome. For this reason, questions regarding the cargo of microparticles, and the signaling pathways involved in their biogenesis, are of interest in attempting to explain the behavior of this autoimmune disease.
Assuntos
Síndrome Antifosfolipídica , Micropartículas Derivadas de Células , Trombose , Animais , Anticorpos Antifosfolipídeos , Feminino , Humanos , Camundongos , Fenótipo , GravidezRESUMO
PROBLEM: Oxidative stress and inflammation are key events leading to pre-eclampsia, involved in several maternal deaths. Low doses of acetylsalicylic acid (ASA) are used in the prevention and treatment of pre-eclampsia. The synthesis of aspirin-triggered lipoxin (ATL) by cyclooxygenase-2 acetylation is an alternative mechanism of ASA, which could explain the effectiveness of ASA treatments. The aim of this study was to evaluate the role of ASA, salicylates, and ATL in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia. METHOD OF STUDY: Plasma from 14 women with pre-eclampsia and 17 normotensive pregnant women was probed for inducing oxidative and inflammatory responses on endothelial cells and U937 promonocytes. The role of ATL, ASA, and salicylic acid (SA) on these events was evaluated. RESULTS: Plasma from women with pre-eclampsia induced TBARS and nitrotyrosine production on endothelial and U937 cells. Pre-treatment with both ATL and ASA decreased the TBARS production, while ATL decreased the nitrotyrosine. Pre-eclamptic plasma augmented the translocation of NF-kB on U937 cells, which decreased by a high dose of ASA and SA. Finally, the pre-eclamptic plasma increased the adhesion of leukocytes-PMN and monocytes-to endothelium, and we were able to determine a state of resolution of inflammation, since ATL decreased the PMN adhesion, and conversely, it increased the monocytes adhesion to endothelium. CONCLUSION: Together, these results suggest that ATL could explain the beneficial actions of ASA and support further research on mechanisms, real efficacy, and rational use of ASA in pre-eclampsia.
Assuntos
Aspirina/uso terapêutico , Lipoxinas/sangue , Estresse Oxidativo/efeitos dos fármacos , Pré-Eclâmpsia/sangue , Ácido Salicílico/sangue , Acetilação , Adolescente , Adulto , Aspirina/sangue , Aspirina/farmacologia , Adesão Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/sangue , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/sangue , Lipoxinas/biossíntese , Lipoxinas/farmacologia , NF-kappa B/metabolismo , Neutrófilos/efeitos dos fármacos , Pré-Eclâmpsia/tratamento farmacológico , Pré-Eclâmpsia/prevenção & controle , Gravidez , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Ácido Salicílico/farmacologia , Substâncias Reativas com Ácido Tiobarbitúrico/análise , Tirosina/análogos & derivados , Tirosina/biossíntese , Células U937 , Adulto JovemRESUMO
Problem Oxidative stress and inflammation are key events leading to pre-eclampsia, involved in several maternal deaths. Low doses of acetylsalicylic acid (ASA) are used in the prevention and treatment of pre-eclampsia. The synthesis of aspirin-triggered lipoxin (ATL) by cyclooxygenase-2 acetylation is an alternative mechanism of ASA, which could explain the effectiveness of ASA treatments. The aim of this study was to evaluate the role of ASA, salicylates, and ATL in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia. Method of study Plasma from 14 women with pre-eclampsia and 17 normotensive pregnant women was probed for inducing oxidative and inflammatory responses on endothelial cells and U937 promonocytes. The role of ATL, ASA, and salicylic acid (SA) on these events was evaluated. Results Plasma from women with pre-eclampsia induced TBARS and nitrotyrosine production on endothelial and U937 cells. Pre-treatment with both ATL and ASA decreased the TBARS production, while ATL decreased the nitrotyrosine. Pre-eclamptic plasma augmented the translocation of NF-kB on U937 cells, which decreased by a high dose of ASA and SA. Finally, the pre-eclamptic plasma increased the adhesion of leukocytes—PMN and monocytes—to endothelium, and we were able to determine a state of resolution of inflammation, since ATL decreased the PMN adhesion, and conversely, it increased the monocytes adhesion to endothelium. Conclusion Together, these results suggest that ATL could explain the beneficial actions of ASA and support further research on mechanisms, real efficacy, and rational use of ASA in pre-eclampsia.
RESUMO
Antecedentes: El síndrome antifosfolípido (SAF) se caracteriza por manifestaciones clínicas de trombosis o morbilidad gestacional y la presencia de anticuerpos antifosfolípidos (aAFL), que se pueden unir al trofoblasto o al endotelio materno, alterando la placentación normal. Objetivo: Evaluar el efecto del suero de mujeres con SAF en un modelo tridimensional de remodelación vascular in vitro. Métodos: Cuantificación sistematizada con el programa Image J y el complemento Angiogenesis Analyzer de la interacción de trofoblasto y endotelio en un modelo tridimensional de remodelación vascular y detección por ELISA del factor de crecimiento del endotelio vascular (VEGF). Se incluyeron 25 mujeres: con morbilidad gestacional y trombosis vascular (MG/TV, n=7) y con morbilidad gestacional únicamente (MG, n=8), ambos grupos con presencia de aAFL; con morbilidad gestacional sin aAFL (MG/aFL-, n=10), y un grupo control de mujeres sanas (SHN, n=7). Resultados: El suero de mujeres con morbilidad gestacional, MG/aAFL-, MG y MG/TV indujo disminución de la angiogénesis endotelial, pero en trofoblasto, únicamente el suero de los dos grupos de mujeres con aAFL tuvo este mismo efecto en concordancia con la reducción del VEGF. El suero de mujeres con MG/aAFL- y MG/TV redujo elementos angiogénicos en el co-cutivo de trofoblasto y endotelio, comparado con el grupo control de SHN. En contraste con el grupo de MG/aAFL-, el suero de mujeres con aAFL, redujo la angiogénesis en células trofoblásticas y endoteliales. Conclusión: El efecto anti-angiogénico de los aAFL se observó focalizado en trofoblasto y el suero del grupo de mujeres con MG/TV indujo mayores efectos deletéreos.
Background: Antiphospholipid syndrome (APS) is characterized by manifestations of thrombosis or pregnancy morbidity and antiphospholipid antibodies (aAPL) which can bind to trophoblast or to maternal endothelium, altering normal placentation. Aims: To evaluate the effect of sera from patients with APS on a three-dimensional in vitro model of vascular remodeling. Methods: Systematic quantification of the interaction between trophoblast and endothelium with the software Image J and the plug-in Angiogenesis Analyzer in a three-dimensional model of vascular remodeling and the detection of vascular endothelial growth factor (VEGF) by ELISA. 25 women divided in three groups were included as follows: with pregnancy morbidity and thrombosis (PM/VT, n=7), pregnancy morbidity (PM, n=8), both groups with aAPL; pregnancy morbidity without aAPL (PM/aAPL-, n=10) and healthy women was used as control (NHS, n=7). Results: Sera from women with gestational morbidity: PM/VT, PM, PM/aAPL-, decreased endothelial angiogenesis, but on trophoblast, only the sera of two groups of women with aAPL had this effect along with reduction of VEGF. Sera from women with PM/aAPL- and PM/VT reduced angiogenesis in the co-culture of trophoblast and endotelial cells compared to NHS. In contrast to PM/aAPL-, sera from women with APS decreased angiogenesis in trophoblastic cells. Conclusions: The anti-angiognic effect of aAPL was focused on trophoblast and sera from PM/VT induced higher deleterious effects.