RESUMO
Gestational diabetes mellitus (GDM) is a world-wide health challenge, which prevalence is expected to increase in parallel to the epidemic of obesity. Children born from GDM mothers have lower levels of docosahexaenoic acid (DHA) in cord blood, which might influence their neurodevelopment. Recently, the membrane transporter Major Family Super Domain 2a (MFSD2a) was associated with the selective transportation of DHA as lysophospholipids. The expression of the DHA membrane transporter MFSD2a is lower in GDM placentas, which could affect materno-fetal DHA transport. Humans with homozygous inactivating mutations in the MFSD2a gene present severe microcephaly and intellectual impairments. Herein, we intended to identify early blood biomarkers that may be of use during pregnancy to monitor the offspring development and the adequate nutritional interventions, such as nutritional supplementation, that may be selected to improve it. We evaluated MFSD2a expression in maternal blood at the third trimester of pregnancy, and its potential relationship with the expression of placental MFSD2a at delivery and child outcomes. Three groups of pregnant women were recruited: 25 controls, 23 GDM with dietary treatment, and 20 GDM with insulin treatment. Maternal and neonatal anthropometric and biochemical parameters were evaluated. MFSD2a was analyzed in placenta, blood and serum. MFSD2a protein expression in maternal blood was significantly lower in GDM groups and correlated with placental MFSD2a and Z-score neonatal head circumference during the first 6 months of life. The cord/maternal serum ratio of DHA, a solid indicator of materno-fetal DHA transport, was reduced in GDM groups and correlated with MFSD2a in maternal blood at the third trimester and in placenta at delivery. This indicates that altered MFSD2a levels in maternal blood during pregnancy might influence placental nutrient transport and fetal neurodevelopment. Furthermore, MFSD2a levels in maternal blood on the third trimester were inversely correlated to DHA in maternal serum lyso-PL. Thus, the level of MFSD2a in maternal blood could be used as a potential biomarker for the early detection of disturbances of MFSD2a expression during pregnancy and the subsequent consequences for the neurodevelopment of the child, as well as it may help to choose the optimal treatment approach for the affected subjects.
Assuntos
Diabetes Gestacional/metabolismo , Feto/anatomia & histologia , Cabeça/anatomia & histologia , Placenta/metabolismo , Simportadores/sangue , Simportadores/metabolismo , Adolescente , Adulto , Estudos de Casos e Controles , Cefalometria , Diabetes Gestacional/sangue , Diabetes Gestacional/dietoterapia , Diabetes Gestacional/tratamento farmacológico , Dieta , Feminino , Sangue Fetal/química , Sangue Fetal/metabolismo , Desenvolvimento Fetal/fisiologia , Feto/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Humanos , Recém-Nascido , Insulina/uso terapêutico , Fenômenos Fisiológicos da Nutrição Materna , Testes para Triagem do Soro Materno , Placenta/química , Gravidez , Terceiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/metabolismo , Simportadores/análise , Adulto JovemRESUMO
BACKGROUND: Maternal blood folate concentrations during pregnancy have been previously linked with DNA methylation patterns, but this has been done predominantly through observational studies. We showed recently in an epigenetic analysis of the first randomized controlled trial (RCT) of folic acid supplementation specifically in the second and third trimesters (the EpiFASSTT trial) that methylation at some imprinted genes was altered in cord blood samples in response to treatment. Here, we report on epigenome-wide screening using the Illumina EPIC array (~ 850,000 sites) in these same samples (n = 86). RESULTS: The top-ranked differentially methylated promoter region (DMR) showed a gain in methylation with folic acid (FA) and was located upstream of the imprint regulator ZFP57. Differences in methylation in cord blood between placebo and folic acid treatment groups at this DMR were verified using pyrosequencing. The DMR also gains methylation in maternal blood in response to FA supplementation. We also found evidence of differential methylation at this region in an independent RCT cohort, the AFAST trial. By altering methylation at this region in two model systems in vitro, we further demonstrated that it was associated with ZFP57 transcription levels. CONCLUSIONS: These results strengthen the link between folic acid supplementation during later pregnancy and epigenetic changes and identify a novel mechanism for regulation of ZFP57. This trial was registered 15 May 2013 at www.isrctn.com as ISRCTN19917787.
Assuntos
Metilação de DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Ácido Fólico/administração & dosagem , Segundo Trimestre da Gravidez/genética , Terceiro Trimestre da Gravidez/genética , Fatores de Transcrição/genética , Adulto , Interação do Duplo Vínculo , Feminino , Ácido Fólico/sangue , Impressão Genômica , Células HCT116 , Humanos , Gravidez , Segundo Trimestre da Gravidez/sangue , Segundo Trimestre da Gravidez/efeitos dos fármacos , Terceiro Trimestre da Gravidez/sangue , Terceiro Trimestre da Gravidez/efeitos dos fármacos , Proteínas Repressoras , Análise de Sequência de DNARESUMO
Este manual está dirigido a la partera tradicional para ayudarle a que haga su trabajo como toda una profesional y así forme parte del gran ejército de cuidado y promoción a la salud. Las parteras tradicionales deben ver a las embarazadas regularmente toda la gestación y también deben capacitarse para atender el parto en condiciones de gran limpieza y aplicar varias medidas que son importantes para la madre y el recién nacido. La tarea no termina allí, ya que las parteras deben hacer la revisión de la madre en el puerperio, fomentar la alimentación al pecho, ver que el niño vaya creciendo normalmente y que reciba sus vacunas. Asimismo, la partera debe aconsejar a la pareja del beneficio que tiene la planificación familiar tanto para la salud de la madre como el bienestar del niño. Por ello el trabajo que realizan las parteras tradicionales es de gran importancia para contribuir a asegurar la salud de la población que vive en el campo y que necesita mucho de sus cuidados