Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.

Adverse fetal environment due to maternal undernutrition or exposure to environmental chemicals alters glucocorticoid (GC) metabolism increasing the risk of metabolic disorders in adulthood. In this study, we investigated the effects of maternal exposure to cadmium (Cd, 50 ppm) during pregnancy in t...

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Autores principales:	Paula Castillo, Freddy Ibáñez, Angélica Guajardo, Miguel N Llanos, Ana M Ronco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d2dba5dca3ab4f0797e25590682dc74e
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spelling	oai:doaj.org-article:d2dba5dca3ab4f0797e25590682dc74e2021-11-18T07:06:35ZImpact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.1932-620310.1371/journal.pone.0044139https://doaj.org/article/d2dba5dca3ab4f0797e25590682dc74e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22957049/?tool=EBIhttps://doaj.org/toc/1932-6203Adverse fetal environment due to maternal undernutrition or exposure to environmental chemicals alters glucocorticoid (GC) metabolism increasing the risk of metabolic disorders in adulthood. In this study, we investigated the effects of maternal exposure to cadmium (Cd, 50 ppm) during pregnancy in the methylation of fetal hepatic glucocorticoid receptor promoter (GR) and the correlation with its expression and that of the DNA methyltransferases (DNMT1a and 3a). We also studied the expression of liver phosphoenolpyruvate carboxykinase (PEPCK) and acyl-CoA oxidase (AOX), two enzymes involved in the metabolism of carbohydrates and lipids respectively. The methylation of the rat GR gene exon 1(10) (GR1(10)) in nucleotides -2536 to -2361 was analyzed by pyrosequencing. Quantitative real time PCR was used to assess hepatic GR, PEPCK and AOX mRNA, and their protein levels using Western blotting analysis. Differential methylation was noted across groups at all CpG sites in the GR exon 1(10) in a sex-dependent manner. In males, CpG were more methylated than the controls (185 ± 21%, p<0.001) but only CpG sites 1,6,7 and 9 showed a significantly different extent of methylation. In addition, a lower expression of GR (mRNA and protein) was found. On the contrary, in females, CpG were less methylated than the controls (62 ± 11%, p<0.05) and overexpressed, affecting PEPCK and AOX expression, which did not change in males. The GR methylation profile correlates with DNMT3a expression which may explain epigenetic sex-dependent changes on GR1(10) promoter induced by Cd treatment. In conclusion, Cd exposure during pregnancy affects fetal liver DNMT3a resulting in sex-dependent changes in methylation and expression of GR1(10). Although these effects do not seem to be directly involved in the low birth weight and height, they may have relevant implications for long-term health.Paula CastilloFreddy IbáñezAngélica GuajardoMiguel N LlanosAna M RoncoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e44139 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paula Castillo Freddy Ibáñez Angélica Guajardo Miguel N Llanos Ana M Ronco Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
description	Adverse fetal environment due to maternal undernutrition or exposure to environmental chemicals alters glucocorticoid (GC) metabolism increasing the risk of metabolic disorders in adulthood. In this study, we investigated the effects of maternal exposure to cadmium (Cd, 50 ppm) during pregnancy in the methylation of fetal hepatic glucocorticoid receptor promoter (GR) and the correlation with its expression and that of the DNA methyltransferases (DNMT1a and 3a). We also studied the expression of liver phosphoenolpyruvate carboxykinase (PEPCK) and acyl-CoA oxidase (AOX), two enzymes involved in the metabolism of carbohydrates and lipids respectively. The methylation of the rat GR gene exon 1(10) (GR1(10)) in nucleotides -2536 to -2361 was analyzed by pyrosequencing. Quantitative real time PCR was used to assess hepatic GR, PEPCK and AOX mRNA, and their protein levels using Western blotting analysis. Differential methylation was noted across groups at all CpG sites in the GR exon 1(10) in a sex-dependent manner. In males, CpG were more methylated than the controls (185 ± 21%, p<0.001) but only CpG sites 1,6,7 and 9 showed a significantly different extent of methylation. In addition, a lower expression of GR (mRNA and protein) was found. On the contrary, in females, CpG were less methylated than the controls (62 ± 11%, p<0.05) and overexpressed, affecting PEPCK and AOX expression, which did not change in males. The GR methylation profile correlates with DNMT3a expression which may explain epigenetic sex-dependent changes on GR1(10) promoter induced by Cd treatment. In conclusion, Cd exposure during pregnancy affects fetal liver DNMT3a resulting in sex-dependent changes in methylation and expression of GR1(10). Although these effects do not seem to be directly involved in the low birth weight and height, they may have relevant implications for long-term health.
format	article
author	Paula Castillo Freddy Ibáñez Angélica Guajardo Miguel N Llanos Ana M Ronco
author_facet	Paula Castillo Freddy Ibáñez Angélica Guajardo Miguel N Llanos Ana M Ronco
author_sort	Paula Castillo
title	Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
title_short	Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
title_full	Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
title_fullStr	Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
title_full_unstemmed	Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
title_sort	impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/d2dba5dca3ab4f0797e25590682dc74e
work_keys_str_mv	AT paulacastillo impactofcadmiumexposureduringpregnancyonhepaticglucocorticoidreceptormethylationandexpressioninratfetus AT freddyibanez impactofcadmiumexposureduringpregnancyonhepaticglucocorticoidreceptormethylationandexpressioninratfetus AT angelicaguajardo impactofcadmiumexposureduringpregnancyonhepaticglucocorticoidreceptormethylationandexpressioninratfetus AT miguelnllanos impactofcadmiumexposureduringpregnancyonhepaticglucocorticoidreceptormethylationandexpressioninratfetus AT anamronco impactofcadmiumexposureduringpregnancyonhepaticglucocorticoidreceptormethylationandexpressioninratfetus
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Impact of cadmium exposure during pregnancy on hepatic glucocorticoid receptor methylation and expression in rat fetus.

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