RESUMO
INTRODUCTION AND OBJECTIVE: The weight gained during pregnancy could determine the immediate and future health of the mother-child dyad. Excessive gestational weight gain (EGWG) due to abnormal adipose tissue (AT) accumulation is strongly associated with adverse perinatal outcomes as gestational diabetes, macrosomia, obesity, and hypertension further in life. Dysregulation of adipokine, AT dysfunction, and an imbalance in the prooxidant-antioxidant systems are critical features in altered AT accumulation. This study was aimed to investigate the association between adipokines and oxidative stress markers in pregnant women and the influence of the GWG on this association. METHODS: Maternal blood samples were obtained in the third trimester of pregnancy (n = 74) and serum adipokines (adiponectin, leptin, and resistin), oxidative damage markers: 8-oxo-2'-deoxyguanosine (8-oxodG), lipohydroperoxides (LOOH), malondialdehyde (MDA), and carbonylated proteins (CP), and glucose a metabolic marker were measured. RESULTS: Women with EGWG had low adiponectin levels than women with adequate weight gain (AWG) or insufficient weight gain (IWG). Multiple linear regression models revealed a positive association between adiponectin and 8-oxodG in women with AWG (B = 1.09, 95% CI: 164-222, p = 0.027) and IWG (B = 0.860, 95% CI: 0.199-1.52, p = 0.013) but not in women with EGWG. In women with EGWG, leptin was positively associated with LOOH (p = 0.018), MDA (p = 0.005), and CP (p = 0.010) oxidative markers. CONCLUSION: Our findings suggest that concurrent mechanisms regulate adipokine production and oxidative stress in pregnant women and that this regulation is influenced by GWG, probably due to an excessive AT accumulation.
Assuntos
Ganho de Peso na Gestação , Adipocinas , Índice de Massa Corporal , Feminino , Macrossomia Fetal , Humanos , Estresse Oxidativo , Gravidez , Resultado da GravidezRESUMO
Preeclampsia (PE) and Intrauterine Growth Restriction (IUGR) are major contributors to perinatal morbidity and mortality. These pregnancy disorders are associated with placental dysfunction and share similar pathophysiological features. The aim of this study was to compare the placental gene expression profiles including mRNA and lncRNAs from pregnant women from four study groups: PE, IUGR, PE-IUGR, and normal pregnancy (NP). Gene expression microarray analysis was performed on placental tissue obtained at delivery and results were validated using RTq-PCR. Differential gene expression analysis revealed that the largest transcript variation was observed in the IUGR samples compared to NP (n = 461; 314 mRNAs: 252 up-regulated and 62 down-regulated; 133 lncRNAs: 36 up-regulated and 98 down-regulated). We also detected a group of differentially expressed transcripts shared between the PE and IUGR samples compared to NP (n = 39), including 9 lncRNAs with a high correlation degree (p < 0.05). Functional enrichment of these shared transcripts showed that cytokine signaling pathways, protein modification, and regulation of JAK-STAT cascade are over-represented in both placental ischemic diseases. These findings contribute to the molecular characterization of placental ischemia showing common epigenetic regulation implicated in the pathophysiology of PE and IUGR.
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Retardo do Crescimento Fetal/genética , Placenta/metabolismo , Pré-Eclâmpsia/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Transcriptoma , Adulto , Peso ao Nascer , Feminino , Retardo do Crescimento Fetal/metabolismo , Humanos , Recém-Nascido , Masculino , Pré-Eclâmpsia/metabolismo , Gravidez , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismoRESUMO
OBJECTIVES: Assess the usefulness of the sFlt-1/PlGF ratio for the differential diagnosis of uncontrolled chronic hypertension vs. superimposed preeclampsia. STUDY DESIGN: We performed a cross-sectional study from 2015 to 2017 and 42 women with initial diagnosis of superimposed preeclampsia were enrolled in the emergency room. After a 12 week follow up patients were grouped as superimposed preeclampsia (Group A) and uncontrolled chronic hypertension (Group B) according to the American College of Obstetricians and Gynecologist criteria. A group of 33 healthy women paired by gestational age were included as controls (Group C). Maternal serum levels of sFlt-1 and PlGF were measured at enrollment, and the ratios of the groups were compared. MAIN OUTCOME MEASURES: Superimposed preeclampsia vs. uncontrolled chronic hypertension. RESULTS: After follow-up, group distribution was 30 women in Group A, 12 women in Group B, and 25 women in Group C. The sFlt-1/PlGF ratio was higher in women with superimposed preeclampsia than in women with uncontrolled chronic hypertension (215.5 vs. 9.65, p < 0.001). The control group displayed lower ratio values (3.66, p < 0.001). The sFlt-1 concentration was higher in Group A than in Group B (7564 vs. 1281 pg/mL, p < 0.001) and the PlGF level was lower in Group A (34.39 vs. 169 pg/mL, p < 0.001). CONCLUSIONS: The sFlt-1/PlGF ratio exhibits good performance for the differential diagnosis of superimposed preeclampsia vs. uncontrolled chronic hypertension.
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Fator de Crescimento Placentário/sangue , Pré-Eclâmpsia/diagnóstico , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Estudos Transversais , Diagnóstico Diferencial , Serviço Hospitalar de Emergência , Feminino , Humanos , Hipertensão/diagnóstico , Pessoa de Meia-Idade , Gravidez , Triagem/métodosRESUMO
Obesity is associated with inflammatory changes and accumulation and phenotype polarization of adipose tissue macrophages (ATMs). Obese pregnant women have alterations in adipose tissue composition, but a detailed description of macrophage population is not available. In this study, we characterized macrophage populations in visceral adipose tissue (VAT) from pregnant women with normal, overweight, and obese pregestational weight. Immunophenotyping of macrophages from VAT biopsies was performed by flow cytometry using CD45 and CD14 as markers of hematopoietic and monocyte linage, respectively, while HLA-DR, CD11c, CD163, and CD206 were used as pro- and anti-inflammatory markers. Adipocyte number and size were evaluated by light microscopy. The results show that pregnant women that were overweight and obese during the pregestational period had adipocyte hypertrophy. Two different macrophage populations in VAT were identified: recruited macrophages (CD45âºCD14âº), and a novel population lacking CD45, which was considered to be a resident macrophages subset (CD45−CD14âº). The number of resident HLA−DRlow/− macrophages showed a negative correlation with body mass index (BMI). Both resident and recruited macrophages from obese women expressed higher CD206 levels. CD11c expression was higher in resident HLA-DR⺠macrophages from obese women. A strong correlation between CD206 and CD11c markers and BMI was observed. Our findings show that being overweight and obese in the pregestational period is associated with adipocyte hypertrophy and specific ATMs populations in VAT.
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Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Adipócitos/citologia , Adipócitos/metabolismo , Adulto , Biomarcadores/metabolismo , Índice de Massa Corporal , Quimiotaxia de Leucócito/imunologia , Estudos Transversais , Feminino , Humanos , Hipertrofia , Imunofenotipagem , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Ativação de Macrófagos/imunologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia , Gravidez , Adulto JovemRESUMO
Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects.