Folic acid supplementation during pregnancy induces sex-specific changes in methylation and expression of placental 11β-hydroxysteroid dehydrogenase 2 in rats

PloS One
Reyna PenaililloAna Maria Ronco

Abstract

In the placenta, 11β-hydroxysteroid dehydrogenase type 2 (11β-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 11β-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 mothe...Continue Reading

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Citations

May 21, 2016·International Journal of Endocrinology·Katarzyna KosickaFranciszek K Główka
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Sep 19, 2018·Cellular and Molecular Life Sciences : CMLS·Ping ZhuKang Sun

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Methods Mentioned

BETA
PCR

Software Mentioned

BiQ Analyzer
STATA
GraphPad Prism

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