PM10 Alters Trophoblast Cell Function and Modulates miR-125b-5p Expression.

Air pollution is one of the largest global environmental health hazards that threaten premature mortality or morbidity. Particulate matter 10 (PM10) has been demonstrated to contribute to several human diseases via dysregulated miRNA expression. Trophoblast cells play a key role in implantation and placentation for a successful pregnancy. Nonetheless, the PM10 associated trophoblast cell functions during pregnancy and miRNA expression are still unknown. Our study showed that PM10 affected HTR-8/SVneo cell viability and also decreased cell proliferation, migration, and invasion. A high concentration of PM10 caused an increase in HTR-8/SVneo cell apoptosis. Treatment with PM10 induced inflammation through the upregulated IL-1ß, IL-6, and TNF-α expression in trophoblast cells. In PM10-treated HTR-8/SVneo cells, miR-125b-5p expression was considerably increased and TXNRD1 was found to be negatively related to miR-125b-5p. Collectively, our findings revealed that PM10 could alter miR-125b-5p expression by targeting TXNRD1 and suppressing trophoblast cell functions. Additional investigations relating to the function of miR-125b-5p and its target on particulate pollution exposure in trophoblast are warranted for future biomarker or effective therapeutic approaches.

The Assessment of Vitamin D Levels in Pregnant Women is not Associated to Fetal Growth Restriction: A Cross Sectional Study.

OBJECTIVE: To assess maternal serum levels of vitamin D in fetuses appropriate for gestational age (AGA), small for gestational age (SGA), and with fetal growth restriction (FGR) according to estimated fetal weight (EFW). METHODS: This cross-sectional study included 87 pregnant women between 26 and 36 weeks of gestation: 38 in the AGA group, 24 in the SGA group, and 25 in the FGR group. Maternal serum vitamin D levels were assessed using the chemiluminescence method. The Fisher exact test was used to compare the results between the groups. RESULTS: The mean ± standard deviation (SD) of maternal age (years) and body mass index (kg/m2) in the AGA, SGA, and FGR groups were 25.26 ± 8.40 / 26.57 ± 4.37; 25.04 ± 8.44 / 26.09 ± 3.94; and 25.48 ± 7.52 / 26.24 ± 4.66, respectively (p > 0.05). The maternal serum vitamin D levels (mean ± SD) of the AGA, SGA, and FGR groups were 22.47 ± 8.35 ng/mL, 24.80 ± 10.76 ng/mL, and 23.61 ± 9.98 ng/mL, respectively, but without significant differences between the groups (p = 0.672). CONCLUSION: Maternal serum vitamin D levels did not present significant differences among pregnant women with AGA, SGA, or FGR fetuses between 26 and 36 weeks of gestation according to EFW.

OBJETIVO: Avaliar o nível sérico materno de vitamina D em fetos adequados para idade gestacional (AIG), pequenos para idade gestacional (PIG) e com restrição de crescimento (RCF) de acordo com a estimativa de peso fetal (EPF). MéTODOS: Realizou-se um estudo transversal envolvendo 87 gestantes entre 26 e 36 semanas, sendo: 38 do grupo AIG, 24 do grupo PIG e 25 do grupo RCF. A dosagem sérica materna de vitamina D foi realizada pelo método de quimiluminescência. Para as comparações entre os grupos, utilizou-se o teste exato de Fisher. RESULTADOS: A média ± desvio-padrão (DP) da idade materna (anos) e do índice de massa corporal (kg/m2) nos grupos AIG, PIG e RCF foram 25,26 ± 8,40 / 26,57 ± 4,37; 25,04 ± 8,44 / 26,09 ± 3,94; e 25,48 ± 7,52 / 26,24 ± 4,66, respectivamente (p > 0,05). A concentração sérica materna de vitamina D (médias ± desvios-padrão) dos grupos AIG, PG e RCF foram 22,47 ± 8,35 ng/ml; 24,80 ± 10,76 ng/ml; e 23,61 ± 9,98 ng/ml, respectivamente, contudo, sem diferenças significativas entre os grupos (p = 0,672). CONCLUSãO: A concentração sérica materna de vitamina D não apresentou diferenças significantes entre gestantes com fetos AIG, PIG ou RCF entre 26 e 36 semanas de acordo com a EPF.

The Assessment of Vitamin D Levels in Pregnant Women is not Associated to Fetal Growth Restriction: A Cross Sectional Study / A avaliação dos níveis de vitamina D em gestantes não está associada à restrição do crescimento fetal: um estudo transversal

Abstract Objective To assess maternal serum levels of vitamin D in fetuses appropriate for gestational age (AGA), small for gestational age (SGA), and with fetal growth restriction (FGR) according to estimated fetal weight (EFW). Methods This cross-sectional study included 87 pregnant women between 26 and 36 weeks of gestation: 38 in the AGA group, 24 in the SGA group, and 25 in the FGR group. Maternal serum vitamin D levels were assessed using the chemiluminescence method. The Fisher exact test was used to compare the results between the groups. Results The mean ± standard deviation (SD) of maternal age (years) and body mass index (kg/m2) in the AGA, SGA, and FGR groups were 25.26 8.40 / 26.57 ± 4.37; 25.04 ± 8.44 / 26.09 ± 3.94; and 25.48 ± 7.52 / 26.24 ± 4.66, respectively (p > 0.05). The maternal serum vitamin D levels (mean ± SD) of the AGA, SGA, and FGR groups were 22.47 ± 8.35 ng/mL, 24.80 ± 10.76 ng/mL, and 23.61 ± 9.98 ng/mL, respectively, but without significant differences between the groups (p = 0.672). Conclusion Maternal serum vitamin D levels did not present significant differences among pregnant women with AGA, SGA, or FGR fetuses between 26 and 36 weeks of gestation according to EFW.

Resumo Objetivo Avaliar o nível sérico materno de vitamina D em fetos adequados para idade gestacional (AIG), pequenos para idade gestacional (PIG) e com restrição de crescimento (RCF) de acordo com a estimativa de peso fetal (EPF). Métodos Realizou-se um estudo transversal envolvendo 87 gestantes entre 26 e 36 semanas, sendo: 38 do grupo AIG, 24 do grupo PIG e 25 do grupo RCF. A dosagem sérica materna de vitamina D foi realizada pelo método de quimiluminescência. Para as comparações entre os grupos, utilizou-se o teste exato de Fisher. Resultados A média ± desvio-padrão (DP) da idade materna (anos) e do índice de massa corporal (kg/m2) nos grupos AIG, PIG e RCF foram 25,26 ± 8,40 / 26,57 ± 4,37; 25,04 ± 8,44 / 26,09 ± 3,94; e 25,48 ± 7,52 / 26,24 ± 4,66, respectivamente (p>0,05). A concentração sérica materna de vitamina D (médias ± desvios-padrão) dos grupos AIG, PG e RCF foram 22,47±8,35 ng/ml; 24,80_10,76 ng/ml; e 23,61 ± 9,98 ng/ml, respectivamente, contudo, sem diferenças significativas entre os grupos (p=0,672). Conclusão A concentração sérica materna de vitamina D não apresentou diferenças significantes entre gestantes com fetos AIG, PIG ou RCF entre 26 e 36 semanas de acordo com a EPF.

Calcium intake in high-risk pregnant women assisted in a high-complexity hospital.

Pregnancy is characterized by physiological changes. One of these changes involves calcium. During this period, an increased in calcium excretion occurs as well as an increased intestinal absorption and renal reabsorption, so that the adequate growth and development of the fetus can happen. Low calcium intake is associated with chronic diseases, such as diabetes and hypertension, which have negative impact on both mother and fetus. This study aimed to evaluate the average calcium intake of high-risk pregnant women, assisted in a clinic of high complexity service and correlated with chronic diseases. To perform this study, it was used a food frequency questionnaire. As a result, high-risk pregnant women showed daily calcium intake lower than the recommended by DRI during this period. Hypertensive or diabetic pregnant women showed lower average intake of calcium. Significant association between calcium intake and nutritional status was not observed. Calcium supplementation was present, however, at low percentage in the groups with hypertensive pregnant women. To analyze the relation between calcium intake and the comorbidities, as well as calcium intake and the nutritional status of the pregnant women, it was used one-way analysis of variance and Bonferroni multiple comparison. Further studies are required for evaluating other parameters that justify the low calcium intake among this population group, and the definition of pathways for the management of the nutritional deficit considering the possible damage to maternal and neonatal health in the short and long term.

Involvement of STAT1 in proliferation and invasiveness of trophoblastic cells.

Trophoblast proliferation and invasion are controlled by cytokines and growth factors present at the implantation site. Members of the Interleukin-6 (IL-6) family of cytokines trigger their effects through activation of intracellular cascades including the Janus Kinase/Signal Transducer and Activator of Transcription (JAK-STAT) pathway. Functions of several STAT molecules in trophoblast cells have been described, but the role of STAT1 remained unclear. Here, potential functions of STAT1 and its activation by Oncostatin M (OSM) have been investigated in an in vitro model. STAT1 expression and phosphorylation were analyzed in human term placenta tissue by immunohistochemistry. HTR-8/SVneo cells (immortalized human extravillous trophoblast cells) were stimulated with OSM, IL-6, IL-11, Leukemia Inhibitory Factor (LIF) and Granulocyte Macrophage Colony-Stimulating Factor. Expression and phosphorylation of STAT1 were analyzed by Western blotting and immunocytochemistry. Fludarabine and STAT1 siRNA were employed for STAT1 depletion. STAT1 transcriptional activity was evaluated by DNA-binding capacity assay. Cell viability and invasion were assessed by MTS and Matrigel assays, respectively. STAT1 was expressed in villous and extravillous trophoblast cells. Low phosphorylation was detectable exclusively in extravillous trophoblast cells. Only OSM and LIF induced phosphorylation of STAT1 in the in vitro model. Challenge with OSM increased cell invasion but not proliferation. Inhibition of STAT1 by fludarabine treatment or STAT1 siRNA transfection reduced cell viability and invasiveness in presence and absence of OSM. These results indicate the potential involvement of STAT1 in the regulation of trophoblast behavior. Furthermore, STAT 1 functions are more efficiently inhibited by blocking its expression than its phosphorylation.

Oncostatin M and leukaemia inhibitory factor trigger signal transducer and activator of transcription 3 and extracellular signal-regulated kinase 1/2 pathways but result in heterogeneous cellular responses in trophoblast cells.

Leukaemia inhibitory factor (LIF) and oncostatin M (OSM) are pleiotropic cytokines present at the implantation site that are important for the normal development of human pregnancy. These cytokines share the cell membrane receptor subunit gp130, resulting in similar functions. The aim of this study was to compare the response to LIF and OSM in several trophoblast models with particular regard to intracellular mechanisms and invasion. Four trophoblast cell lines with different characteristics were used: HTR-8/SVneo, JEG-3, ACH-3P and AC1-M59 cells. Cells were incubated with LIF, OSM (both at 10ngmL(-1)) and the signal transducer and activator of transcription (STAT) 3 inhibitor S3I-201 (200µM). Expression and phosphorylation of STAT3 (tyr(705)) and extracellular regulated kinase (ERK) 1/2 (thr(202/204)) and the STAT3 DNA-binding capacity were analysed by Western blotting and DNA-binding assays, respectively. Cell viability and invasiveness were assessed by the methylthiazole tetrazolium salt (MTS) and Matrigel assays. Enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 was investigated by zymography. OSM and LIF triggered phosphorylation of STAT3 and ERK1/2, followed by a significant increase in STAT3 DNA-binding activity in all tested cell lines. Stimulation with LIF but not OSM significantly enhanced invasion of ACH-3P and JEG-3 cells, but not HTR-8/SVneo or AC1-M59 cells. Similarly, STAT3 inhibition significantly decreased the invasiveness of only ACH-3P and JEG-3 cells concomitant with decreases in secreted MMP-2 and MMP-9. OSM shares with LIF the capacity to activate ERK1/2 and STAT3 pathways in all cell lines tested, but their resulting effects are dependent on cell type. This suggests that LIF and OSM may partially substitute for each other in case of deficiencies or therapeutic interventions.

Atenção à gestante e à puérpera no SUS - SP: manual técnico do pré-natal e e puérperio / Pregnant woman attention at SUS-SP: prenatal care and postpartum period technical manual

Embora, nas últimas décadas, a cobertura de atenção ao pré-natal tenha aumentado, garantir sua qualidade permanece como o maior desafio. Essa melhoria da qualidade, no patamar em que estamos, refere-se a uma mudança sensível na atitude dos profissionais de saúde e na eficiência e presteza dos serviços. É preciso potencializar os recursos humanos e materiais existentes no Estado de São Paulo para o progressivo enfrentamento da morbimortalidade materna e perinatal. É verdade, também, que resultados nesse campo dependem de outros fatores, relativos ao desenvolvimento econômico, social e humano de cada região, que terminam por conferir maior ou menor suporte ás mulheres no momento da reprodução. A qualificação permanente da atenção ao pré-natal, ao parto e ao puerpério deve sempre ser perseguida na perspectiva de garantir uma boa condição de saúde tanto para a mulher quanto para o recém-nascido, bem como de possibilitar à mulher uma experiência de vida gratificante nesse período. Para isso, é necessário que os profissionais envolvidos em qualquer instância do processo assistencial estejam conscientes da importância de sua atuação e da necessidade de aliarem o conhecimento técnico específico ao compromisso com um resultado satisfatório da atenção, levando em consideração o significado desse resultado para cada mulher. A consulta pré-natal, para muitas mulheres, constitui-se na única oportunidde que possuem para verificar seu estado de saúde; assim, deve-se considerá-la também como uma chance para que o sistema possa atuar integralmente na promoção e, eventualmente, na recuperação de sua saúde. Feitas essas considerações, e respeitando-se as orientações constantes no Pacto pela Vida e as decisões emandad do Plano Estadual de Saúde de São Paulo, definem-se as seguintes diretrizes para nortear a atenção ao pré-natal e ao puerpério...

Atenção à gestante e à puérpera no SUS - SP: manual técnico do pré-natal e e puérperio / Pregnant woman attention at SUS-SP: prenatal care and postpartum period technical manual

Embora, nas últimas décadas, a cobertura de atenção ao pré-natal tenha aumentado, garantir sua qualidade permanece como o maior desafio. Essa melhoria da qualidade, no patamar em que estamos, refere-se a uma mudança sensível na atitude dos profissionais de saúde e na eficiência e presteza dos serviços. É preciso potencializar os recursos humanos e materiais existentes no Estado de São Paulo para o progressivo enfrentamento da morbimortalidade materna e perinatal. É verdade, também, que resultados nesse campo dependem de outros fatores, relativos ao desenvolvimento econômico, social e humano de cada região, que terminam por conferir maior ou menor suporte às mulheres no momento da reprodução. A qualificação permanente da atenção ao pré-natal, ao parto e ao puerpério deve sempre ser perseguida na perspectiva de garantir uma boa condição de saúde tanto para a mulher quanto para o recém-nascido, bem como de possibilitar à mulher uma experiência de vida gratificante nesse período. Para isso, é necessário que os profissionais envolvidos em qualquer instância do processo assistencial estejam conscientes da importância de sua atuação e da necessidade de aliarem o conhecimento técnico específico ao compromisso com um resultado satisfatório da atenção, levando em consideração o significado desse resultado para cada mulher. A consulta pré-natal, para muitas mulheres, constitui-se na única oportunidade que possuem para verificar seu estado de saúde; assim, deve-se considerá-la também como uma chance para que o sistema possa atuar integralmente na promoção e, eventualmente, na recuperação de sua saúde. Feitas essas considerações, e respeitando-se as orientações constantes no Pacto pela Vida e as decisões emanadas do Plano Estadual de Saúde de São Paulo, definem-se as seguintes diretrizes para nortear a atenção ao pré-natal e ao puerpério...

Estudo da morfologia vascular do leito placentário na hipertensão arterial crônica / Morphology of the vascular placental bed in chronic arterial hypertension

OBJETIVO: Analisar os padrões histopatológicos das artérias do leito placentário em gestações complicadas por hipertensão arterial crônica (HAC) comparando-os com o de grávidas normais. MÉTODOS: Biópsias de leito placentário, segundo técnica de Robertson et al.1, foram realizadas em pacientes com idade gestacional igual ou superior a 28 semanas, submetidas a cesárea, após a dequitação. O grupo controle (GC) foi composto por 25 pacientes normais e o grupo de estudo composto por 13 pacientes com HAC leve (HL), 11 pacientes com HAC moderada (HM) e 11 pacientes com HAC grave (HG). As classes de hipertensão foram consideradas leve (PAD 90 - 100 mmHg), moderada (PAD 100 - 110 mmHg) e grave (PAD3 > 110mmHg). Os padrões histológicos das artérias espiraladas foram classificados em: padrão inalterado, modificações fisiológicas, desorganização da camada média, alterações hiperplásicas, necrose e aterose aguda. RESULTADOS: 1) Os achados anormais foram predominantes no grupo de hipertensas, sendo mais freqüente nos grupos HM e HG. 2) O achado anormal mais prevalente foi a desorganização da camada média, com distribuição semelhante nos grupos HM e HG. 3) Os padrões normais ocorreram nos grupos GC e HL, com distribuição semelhante entre si.

OBJECTIVES: To analyze histopathological patterns of placental bed arteries in pregnancies complicated by chronic arterial hypertension. Alterations were considered according to clinical classification of the hypertensive disorders as mild (MG); moderate (MoG) and severe (SG) for comparison with uncomplicated pregnancies, control group (CG). METHODS: Placental bed biopsy was performed in 60 pregnant women; the study group was comprised of pregnant women with hypertension, subdivided in 13 with severe chronic hypertension (CH), 11 with moderate CH and 11 with mild CH, and results were compared to 25 placental bed biopsies from uncomplicated pregnancies. All the pregnant women had a gestational age of at least 28 weeks of gestation with a live fetus and were submitted to cesarean section. Hypertension was considered mild with diastolic blood pressure (DBP) 90 I? 100 mmHg, moderate DBP 100 I? 110 mmHg and severe DBP = 110 mmHg. Placental bed variables selected for histological analysis were: unaltered patterns, physiological changes, medial layer disorganization, medial and intimal hyperplasic changes, acute necrosis and atherosis. RESULTS: In cases with SG and MoG there was predominance of abnormal histophysiological findings: medial layer disorganization and hyperplasic changes, with a statistically significant difference when compared to MG and CG. Alteration in the medial layer was observed in these cases. The normal pattern, unaltered patterns and physiologic changes were more frequent in CG and MG. Physiological changes were the most usual finding, further, there was no acute necrosis or atherosis. CONCLUSION: 1. Abnormal histophysiological findings were predominant in hypertensive pregnant women compared to the normotensive ones; 2. These patterns were more frequent, according to the severity of the hypertensive disorders: Severe, Moderate and Mild; 3. More significant abnormal findings were a change in the medial layer, mainly in...

A polêmica da histerorrafia na operação cesariana / The polemic of hysterorraphy on caesarean section

A histerorrafia no parto cesáreo constitui tempo cirúrgico nobre, pois a adequada cicatrização uterina poderá evitar as nefastas conseqüências da ruptura uterina, para a mãe e concepto, em futura gestação e parto. Essa técnica de sutura, entretanto, não apresenta uniformidade plena na literatura. Os métodos subsidiários de avaliação do estado da cicatriz uterina também não têm se mostrado eficientes e práticos. Há preferência pela utilização de fios absorvíveis sintéticos, principalmente em função da menor reação tecidual que promovem. Não é consenso, mas prevalece a opinião de que um único plano com sutura contínua tem melhor relação custo/benefício. A técnica de histerorrafia na cesariana também poderá variar de acordo com o grau de urgência e volume de sangramento no momento do procedimento.

The hysteroraphy in the caesarean section constitutes a right time surgical procedure, as the adequate uterine cicatrization will prevent the uterine rupture undesirable effects for the mother and concepto, future gestation and childbirth. This suture technique, however, does not present full uniformity in literature. The subsidiary evaluation methods on the state of the uterine scar have not been shown efficient and practical. There is preference for the synthetic absorvible thread use, mainly in relation to the lesser tecidual reaction that is promoted. It is not a consensus, but the prevailing opinion is that there is better cost/benefit relation in an only plan with continuous suture. The technique of hysterorraphy in the cesarian section may also vary according to the urgency level and bleeding volume at the procedure time.

[Morphology of the vascular placental bed in chronic arterial hypertension]. / Estudo da morfologia vascular do leito placentário na hipertensão arterial crônica.

OBJECTIVES: To analyze histopathological patterns of placental bed arteries in pregnancies complicated by chronic arterial hypertension. Alterations were considered according to clinical classification of the hypertensive disorders as mild (MG); moderate (MoG) and severe (SG) for comparison with uncomplicated pregnancies, control group (CG). METHODS: Placental bed biopsy was performed in 60 pregnant women; the study group was comprised of pregnant women with hypertension, subdivided in 13 with severe chronic hypertension (CH), 11 with moderate CH and 11 with mild CH, and results were compared to 25 placental bed biopsies from uncomplicated pregnancies. All the pregnant women had a gestational age of at least 28 weeks of gestation with a live fetus and were submitted to cesarean section. Hypertension was considered mild with diastolic blood pressure (DBP) 90 I? 100 mmHg, moderate DBP 100 I? 110 mmHg and severe DBP=110 mmHg. Placental bed variables selected for histological analysis were: unaltered patterns, physiological changes, medial layer disorganization, medial and intimal hyperplasic changes, acute necrosis and atherosis. RESULTS: In cases with SG and MoG there was predominance of abnormal histophysiological findings: medial layer disorganization and hyperplasic changes, with a statistically significant difference when compared to MG and CG. Alteration in the medial layer was observed in these cases. The normal pattern, unaltered patterns and physiologic changes were more frequent in CG and MG. Physiological changes were the most usual finding, further, there was no acute necrosis or atherosis. CONCLUSION: 1. Abnormal histophysiological findings were predominant in hypertensive pregnant women compared to the normotensive ones; 2. These patterns were more frequent, according to the severity of the hypertensive disorders: Severe, Moderate and Mild; 3. More significant abnormal findings were a change in the medial layer, mainly in the group with severe hypertensive disorders; 4. The groups with moderate and severe hypertensive disorders when compared had similar results; 5. The normal histological pattern was higher in the control group and patients with mild hypertensive disorders and disclosed a similarity between them 6. The most usual pattern was physiologic changes, which was more frequent in the control group.

Septostomy with amniodrainage in the treatment of twin-to-twin transfusion syndrome: a 16-case report.

OBJECTIVE: To report the treatment results of 16 monochorionic and diamniotic gestations cases, which had complications due to the twin-to-twin transfusion syndrome (TTTS), the neonatal and other possible complications of the septostomy associated to the amniodrainage. METHOD: Based on ultrasonographic findings, 16 pregnant women were diagnosed with the twin-to-twin transfusion syndrome (TTTS). These cases were divided in two groups: one of them included the fetuses without hydrops and the second included the "recipient" fetuses with hydrops. The therapy measures included septostomy with or without amniodrainage. The following parameters were evaluated: gestational age at the time the septostomy was performed, volume of drained amniotic fluid, gestational age at delivery, birth weight, postnatal evolution, and procedure complications. RESULTS: The average gestational age for this procedure was of 23.6 weeks (from 14 weeks and 1 day to 33 weeks). The gestational age for the septostomy until the delivery was of 8.18 weeks (from 1.0 to 21.3 weeks). The survival rate in the group without hydrops was of 68.7%, while in the second group it was of 25%. Some of the complications were as follows: two cases of premature membrane rupture and one case of preterm labor. CONCLUSION: Septostomy with amniodrainage, when performed on the initial stages and on earlier gestational ages has good perinatal results.