Folic Acid Supplementation during Pregnancy Induces Sex-Specific Changes in Methylation and Expression of Placental 11 beta-Hydroxysteroid Dehydrogenase 2 in Rats

Artículo de publicación ISIIn the placenta, 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) limits fetal glucocorticoid exposure and its inhibition has been associated to low birth weight. Its expression, encoded by the HSD11B2 gene is regulated by DNA methylation. We hypothesized that maternal diets supplemented with folic acid (FA) during pregnancy modify the expression of placental HSD11B2 through gene methylation. Wistar rats were fed with high (8 mg/kg) or normal low (1mg/kg, control) levels of FA during pregnancy. Concentrations of mRNA and protein in placentas were determined by qRT-PCR and Western blot respectively. Methylation in five CpG sites of the placental HSD11B2 promoter (-378 to -275) was analyzed by bacterial cloning and subsequent sequencing. In the FA-supplemented group, mRNA and protein levels of 11 beta-HSD2 decreased by 58% and increased by 89%, respectively, only in placentas attached to males. In controls, most CpG sites were not methylated except for the CpG2 site which was 80% methylated. CpG2 methylation level increased under the FA treatment; however, only in placentas attached to females was this increase significant (113%). This change was not related to HSD11B2 expression. Fetal weight of females from FA-supplemented mothers was 6% higher than females from control mothers. In conclusion, this is the first study reporting that FA over supplementation during pregnancy modifies the placental HSD11B2 gene expression and methylation in a sex-dependent manner, suggesting that maternal diets with high content of FA can induce early sex-specific responses, which may lead to long-term consequences for the offspring.Fondo Nacional de Ciencia y Tecnologia, Gobierno de Chile (Fondecyt) 113018

Suplementación prenatal con omega 3 y su efecto en complicaciones durante el embarazo

During pregnancy, omega 3 supplementation has raised its popularity due to evidence that it would show not only benefits in the neural and visual development of the unborn child, but also in the prevention of obstetrical pathologies associated with of perinatal morbidity and mortality. Omega 3 polyunsaturated fatty acids (PUFAs), specifically, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), possess anti-inflammatory, vasodilatory and anti-aggregating properties, which have led to the use of PUFAs in the prevention of cardiovascular diseases. In this review, we detail the effects of omega 3 supplementation on different aspects of pregnancy such as prevention of preterm birth, pre-eclampsia, postpartum depression, and improved metabolism during gestational diabetes. Although there are several randomized clinical trials using omega-3 supplementation during pregnancy, the evidence remains inconclusive, due to variability in dosage and administration time. Certainly, a greater number of high-quality studies including randomized clinical trials are necessary to determine the impact of omega 3 supplementation during pregnancy in the prevention of obstetric pathologiesDurante los últimos años se ha incentivado la suplementación con omega 3 durante el embarazo principalmente debido a la evidencia que mostraría beneficios en el desarrollo neuronal y visual del hijo en gestación, y a la prevención de patologías obstétricas asociadas a un aumento de la morbi-mortalidad perinatal. Los ácidos grasos poliinsaturados (PUFAs) omega 3, específicamente el ácido eicosapentaenoico (EPA) y el ácido docosahexaenoico (DHA), poseen propiedades antiinflamatorias, vasodilatadoras, además de propiedades anti-agregantes, las cuales han estimulado el uso de PUFAs en la prevención de enfermedades cardiovasculares. En esta revisión detallamos los efectos de la suplementación con omega 3 en diferentes aspectos del embarazo tales como la prevención del parto prematuro, preeclampsia, depresión post-parto y mejora del metabolismo durante la diabetes gestacional. Si bien existen diversos ensayos clínicos randomizados que estudian la suplementación con omega 3 durante la gestación, la evidencia sigue siendo no concluyente, debido a la variabilidad de las dosis y tiempo de administración. Ciertamente, un mayor número de estudios de calidad son necesarios para determinar el real impacto de la suplementación con omega 3 durante la gestación en la prevención de patologías obstétrica

Fatty acid and lipid metabolism in liver of pregnant mice and their offspring is influenced by unbalanced folates/vitamin B12 diets

Micronutrients (folates and vitamin B12) and long chain polyunsaturated fatty acids (LC-PUFAs) are linked through the one carbon cycle. We studied the effects of pre and postnatal high FA/low B12 diets (HFLB12) on hepatic fatty acid metabolism. Pregnant C57BL/6 mice were divided in two groups: control (2 mg folic acid: FA/25 mu g vitamin B12/Kg food) and HFLB12 diets (8 mg FA/5 mu g vitamin B12/Kg food). Offspring continued on the same diets until 60 days old. We determined hepatic fatty acid profile in dams and offspring and the expression of PPARa, Cpt-1, Acox-1 and Fas and the enzymatic activity of desaturases, all involved in lipid metabolism. In liver of dams, the HFHB12 diet decreased total fatty acids and desaturase activities; in offspring, effects were opposite, being more noticeable in females. Prenatal and postnatal unbalanced folic acid/B12 diets play a crucial role in regulating genes and enzymes involved in lipid metabolism in liver of dams and their offspring in adulthood.Comisión Nacional de Investigación Científica y Tecnológica (CONICYT), CONICYT FONDECYT: 1130188, 11140174. Grant Abraham Stekel 2016. CONICYT-PCHA/Doctorado Nacional 2017-21170259

The role of long non-coding rnas in trophoblast regulation in preeclampsia and intrauterine growth restriction

10.3390/genes12070970Genes12797

Supplementation of omega 3 during pregnancy and the risk of preterm birth: A systematic review and meta-analysis

10.3390/nu13051704Nutrients135170

Identification of LOC101927355 as a Novel Biomarker for Preeclampsia

Preeclampsia, a disorder with a heterogeneous physiopathology, can be attributed to maternal, fetal, and/or placental factors. Long non-coding RNAs (lncRNAs) refer to a class of non-coding RNAs, the essential regulators of biological processes; their differential expression has been associated with the pathogenesis of multiple diseases. The study aimed to identify lncRNAs, expressed in the placentas and plasma of patients who presented with preeclampsia, as potential putative biomarkers of the disease. In silico analysis was performed to determine lncRNAs differentially expressed in the placentas of patients with preeclampsia, using a previously published RNA-Seq dataset. Seven placentas and maternal plasma samples collected at delivery from preterm preeclamptic patients (≤37 gestational weeks of gestation), and controls were used to validate the expression of lncRNAs by qRT-PCR. Six lncRNAs were validated and differentially expressed (p < 0.05) in the preeclampsia and control placentas: UCA1 and HCG4 were found upregulated, and LOC101927355, LINC00551, PART1, and NRAD1 downregulated. Two of these lncRNAs, HCG4 and LOC101927355, were also detected in maternal plasma, the latter showing a significant decrease (p = 0.03) in preeclamptic patients compared to the control group. In silico analyses showed the cytoplasmic location of LOC101927355, which suggests a role in post-transcriptional gene regulation. The detection of LOC101927355 in the placenta and plasma opens new possibilities for understanding the pathogenesis of preeclampsia and for its potential use as a biomarker