Placental Expression of Imprinted Genes, Overall and in Sex-Specific Patterns, Associated with Placental Cadmium Concentrations and Birth Size.

Autor: Everson TM; Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, Georgia, USA., Marable C; Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, Georgia, USA., Deyssenroth MA; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Punshon T; Department of Biological Sciences, Dartmouth College, Hanover, New Hampshire, USA., Jackson BP; Department of Earth Sciences, Dartmouth College, Hanover, New Hampshire, USA., Lambertini L; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Karagas MR; Department of Epidemiology, Geisel School of Medicine at Dartmouth College, Hanover, New Hampshire, USA.; Children's Environmental Health and Disease Prevention Research Center at Dartmouth Geisel School of Medicine, Lebanon, New Hampshire, USA., Chen J; Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, New York, USA., Marsit CJ; Department of Environmental Health, Rollins School of Public Health at Emory University, Atlanta, Georgia, USA.; Department of Epidemiology, Rollins School of Public Health at Emory University, Atlanta, Georgia, USA.
Jazyk: angličtina
Zdroj: Environmental health perspectives [Environ Health Perspect] 2019 May; Vol. 127 (5), pp. 57005.
DOI: 10.1289/EHP4264
Abstrakt: Background: Prenatal cadmium (Cd) exposure has been recognized to restrict growth, and male and female fetuses may have differential susceptibility to the developmental toxicity of Cd. Imprinted genes, which exhibit monoallelic expression based on parent of origin, are highly expressed in placental tissues. The function of these genes is particularly critical to fetal growth and development, and some are expressed in sex-specific patterns.
Objectives: We aimed to examine whether prenatal Cd associates with the expression of imprinted placental genes, overall or in fetal sex-specific patterns, across two independent epidemiologic studies.
Methods: We tested for Cd–sex interactions in association with gene expression, then regressed the placental expression levels of 74 putative imprinted genes on placental log-Cd concentrations while adjusting for maternal age, sex, smoking history, and educational attainment. These models were performed within study- and sex-specific strata in the New Hampshire Birth Cohort Study (NHBCS; [Formula: see text]) and the Rhode Island Child Health Study (RICHS; [Formula: see text]). We then used fixed-effects models to estimate the sex-specific and overall associations across strata and then examine heterogeneity in the associations by fetal sex.
Results: We observed that higher Cd concentrations were associated with higher expression of distal-less homeobox 5 ( DLX5 ) ([Formula: see text]), and lower expression of h19 imprinted maternally expressed transcript ( H19 ) ([Formula: see text]) and necdin, MAGE family member ( NDN ) ([Formula: see text]) across study and sex-specific strata, while three other genes [carboxypeptidase A4 ( CPA4 ), growth factor receptor bound protein 10 ( GRB10 ), and integrin-linked kinase ( ILK )] were significantly associated with Cd concentrations, but only among female placenta ([Formula: see text]). Additionally, the expression of DLX5 , H19 , and NDN , the most statistically significant Cd-associated genes, were also associated with standardized birth weight z -scores.
Discussion: The differential regulation of a set of imprinted genes, particularly DLX5 , H19 , and NDN , in association with prenatal Cd exposure may be involved in overall developmental toxicity, and some imprinted genes may respond to Cd exposure in a manner that is specific to infant gender. https://doi.org/10.1289/EHP4264.
Databáze: MEDLINE
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