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1.
Epigenomics ; 13(4): 257-269, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33471580

RESUMEN

Aim: This study aims to examine the DNA methylation (DNAm) and expression patterns of genes associated with placental angiogenesis in preeclampsia. Materials & methods: DNAm and expression were examined in normotensive (n = 100) and preeclampsia (n = 100) women using pyrosequencing and quantitative real-time PCR respectively. Results: Hypomethylation at several CpGs was observed in PlGF and FLT-1 in women with preeclampsia compared to normotensive controls. PlGF expression was lower in women with preeclampsia while FLT-1 expression was comparable. DNAm at various CpGs was negatively correlated with expression in both the genes and were associated with maternal blood pressure and birth outcomes. Conclusion: DNAm and expression of angiogenic factors in placentae are differentially regulated in preeclampsia and influence birth outcomes.


Asunto(s)
Metilación de ADN/fisiología , Factor de Crecimiento Placentario/metabolismo , Placenta/metabolismo , Preeclampsia/metabolismo , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Adulto , Secuencia de Bases , Estudios de Casos y Controles , Femenino , Humanos , Embarazo , Adulto Joven
2.
Nutr Res ; 86: 37-49, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33482597

RESUMEN

Preeclampsia is a pregnancy-specific disorder, leading to maternal and infant morbidity and mortality. Abnormal placentation has been reported in preeclampsia. Nutrients like vitamin D and long-chain polyunsaturated fatty acids (LCPUFA) are known to play a role in placental development. In an animal model, we have previously demonstrated that maternal vitamin D deficiency increases the thromboxane/prostacyclin ratio and contributes to inflammation and vasoconstriction. We hypothesize that maternal vitamin D status influences placental LCPUFA metabolism through alterations in one carbon metabolism in women with preeclampsia. To test this hypothesis, we recruited 69 normotensive control (NC) women and 50 women with preeclampsia. Women with preeclampsia had lower placental protein and mRNA levels of cystathionine-ß-synthase (CBS), higher plasma malondialdehyde (MDA) levels and higher levels of arachidonic acid (AA) and total omega-6 fatty acids in the placenta. Women with preeclampsia also demonstrated higher placental mRNA levels of cyclooxygenase-2 (COX-2) as compared to NC women. Maternal 25(OH)D levels were negatively associated with maternal plasma MDA levels. Placental vitamin D receptor (VDR) levels were positively associated with CBS while maternal MDA levels were positively associated with serum levels of thromboxane-B2 (TXB2) levels. Our findings indicate that vitamin D deficiency increases oxidative stress through alterations in one carbon metabolism to influence pro-inflammatory omega-6 metabolic pathway in the placenta. This study demonstrates a possible mechanism through which vitamin D deficiency can result in an imbalance in the LCPUFA metabolites and contribute to placental inflammation and endothelial dysfunction in preeclampsia.


Asunto(s)
Ácidos Grasos Insaturados/metabolismo , Preeclampsia/metabolismo , Resultado del Embarazo , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/metabolismo , Adolescente , Adulto , Estudios Transversales , Ácidos Grasos/metabolismo , Femenino , Humanos , Recién Nacido , Malondialdehído/sangre , Estrés Oxidativo , Placenta/metabolismo , Preeclampsia/sangre , Embarazo , Receptores de Calcitriol/metabolismo , Tromboxano B2/sangre , Vitamina D/análogos & derivados , Vitamina D/sangre , Deficiencia de Vitamina D/sangre , Adulto Joven
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