Prenatal exposure to organochlorine compounds and neuropsychological development up to two years of life

Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain.
Environment international (Impact Factor: 5.56). 05/2012; 45(1):72-7. DOI: 10.1016/j.envint.2012.04.009
Source: PubMed


Polychlorinated biphenyls (PCB), hexachlorobenzene (HCB), and dichlorodiphenyl dichloroethylene (pp'DDE) are persistent, bioaccumulative, and toxic environmental pollutants with potential neurotoxic effects. Despite a growing body of studies investigating the health effects associated with these compounds, their specific effects on early neuropsychological development remain unclear. We investigated such neuropsychological effects in a population-based birth cohort based in three regions in Spain (Sabadell, Gipuzkoa, and Valencia) derived from the INMA [Environment and Childhood] Project. The main analyses in this report were based on 1391 mother-child pairs with complete information on maternal levels of organochlorine compounds and child neuropsychological assessment (Bayley Scales of Infant Development) at age 14 months. We found that prenatal PCB exposure, particularly to congeners 138 and 153, resulted in impairment of psychomotor development (coefficient=-1.24, 95% confidence interval=-2.41, -0.07), but found no evidence for effects on cognitive development. Prenatal exposure to pp'DDE or HCB was not associated with early neuropsychological development. The negative effects of exposure to PCBs on early psychomotor development suggest that the potential neurotoxic effects of these compounds may be evident even at low doses.

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Available from: Aritz Aranbarri
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    • "Polychlorinated biphenyls (PCBs) are worldwide environmental pollutants consisting of 209 congeners whose toxicity is related to the position of chlorine atoms on their phenyl rings and their planarity (ortho and non-ortho positions). Health effects associated with exposure to PCBs include carcinogenicity (Ludewig and Robertson, 2013; Porta et al., 2007), genotoxicity (Viganò et al., 2002; Jacobus et al., 2010), neurotoxicity (Crinnion, 2009; Forns et al., 2012; Ribas-Fitó et al., 2001), and reproductive toxicity (Nieminen et al., 2013). In the past, the toxic effects of PCBs have been mostly attributed to the coplanar or dioxin-like (DL-PCBs) compounds that bind to AhR (Kafafi et al., 1993). "
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    ABSTRACT: Previously, we evaluated the effects of lactational exposure to a representative mixture of the six indicator non-dioxin-like polychlorinated biphenyls (∑6 NDL-PCBs) at low levels on the neurobiological changes and developmental/behavioral performances in mice. In this study, we analyzed the global gene expression profile in cerebellar neurons isolated from male mice presenting the most significant induction of anxiety-like behavior in our previous study (10ng/kg ∑6 NDL-PCBs). Our results revealed changes in the expression of 16658 genes in the neurons of the exposed mice. Among these, 693 upregulated [fold change (FC)>2; p<0.05] and 665 downregulated (FC<2; p<0.05) genes were statistically linked to gene ontology terms (GO). Overexpressed genes belonged to GO terms involved with the cell cycle, DNA replication, cell cycle checkpoint, response to DNA damage stimulus, regulation of RNA biosynthetic processes, and microtubule cytoskeleton organization. Downregulated genes belonged to terms involved with the transmission of nerve impulses, projection neurons, synapse hands, cell junctions, and regulation of RNA biosynthetic processes. Using qPCR, we quantified gene expression related to DNA damage and validated the transcriptomic study, as a significant overexpression of Atm-Atr Bard1, Brca2, Fancd2, Figf, Mycn, p53 and Rad51 was observed between groups (p<0.001). Finally, using immunoblots we determined the expression level of six selected proteins. We found that changes in the protein expression of Atm Brca1, p53, Kcnma1, Npy4r and Scn1a was significant between exposed and control groups (p<0.05), indicating that the expression pattern of these proteins agreed with the expression pattern of their genes by qPCR, further validating our transcriptomic findings. In conclusion, our study showed that early life exposure of male mice to a low level of ∑6 NDL-PCBs induced p53-dependent responses to cellular stress and a decrease in the expression of proteins involved in the generation, conduction, and transmission of electrical signals in neurons. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Full-text · Article · Dec 2014 · Toxicology
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    • "Several studies have evidenced the transplacental transfer of xenoestrogens including POPs, flame retardants and arsenic, which only weakly or fail to bind to α-fetoprotein, the fetal form of serum albumin (Frederiksen et al., 2010; Pilsner et al., 2012; Tan et al., 2009). Exposure in utero has been related to a number of adverse health endpoints in children, including a higher risk for overweight, alterations in psychomotor and cognitive development or urogenital abnormalities in male newborns (Forns et al., 2012; Palmer et al., 2009; Puertas et al., 2010; Valvi et al. 2013), and several studies have reported sex specific effects occurring by mechanisms that remain poorly understood (Fernandez et al., 2007; Papadopoulou et al., 2013; Vafeiadi et al., 2013; Valvi et al., 2012). A number of in vivo and in vitro studies and a few human investigations have shown effects of EDCs, mainly pesticides, on different epigenetic marks including DNA methylation as reviewed by Collotta et al. (2013) (Collotta et al., 2013), and there is some evidence in animal models of transgenerational inheritance of epigenetic alterations and disease-associated states due to EDC exposure (Guerrero-Bosagna et al., 2012; Guerrero-Bosagna et al., 2013; Manikkam et al., 2013; Skinner et al., 2013). "
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    ABSTRACT: Background: Prenatal exposure to endocrine disrupting compounds (EDCs) has previously shown to alter epigenetic marks. Objectives: In this work we explore whether prenatal exposure to mixtures of xenoestrogens has the potential to alter the placenta epigenome, by studying DNA methylation in retrotransposons as a surrogate of global DNA methylation. Methods: The biomarker total effective xenoestrogen burden (TEXB) was measured in 192 placentas from participants in the longitudinal INMA Project. DNA methylation was quantitatively assessed by bisulfite pyrosequencing on 10 different retrotransposons including 3 different long interspersed nuclear elements (LINEs), 4 short interspersed nuclear elements (SINEs) and 3 human endogenous retroviruses (HERVs). Associations were tested using linear mixed-effects regression models and sex interaction was evaluated. Results: A significant sex interaction was observed for AluYb8 (p-value for interaction <0.001, significant at Bonferroni corrected p-value threshold of 0.0025). Boys with the highest TEXB-alpha levels of exposure (third tertile) presented on average a decrease of 0.84% in methylation compared to those in the first tertile (p-value < 0.001), while no significant effects were found in girls (p-value = 0.134). Conclusions: Our findings suggest that boys may be more susceptible to the effect of exposure to xenoestrogens during prenatal development, producing shifts in DNA methylation of certain sensitive genomic repetitive sequences in a tissue important for fetal growth and development.
    Full-text · Article · Jun 2014 · Environment International
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    • "Nowadays their synthesis is severely restricted or forbidden, but they are still found in the environment and in human tissues (Carrizo et al. 2006; Grimalt et al. 2001; Simonich and Hites 1995) as consequence of their high persis­ tence and liposolubility. In utero exposure to background POP levels has been associ­ ated with evidence of endocrine disruption (Herbstman et al. 2008; Lopez­Espinosa et al. 2010), neurodevelopmental disorders (Forns et al. 2012; Herbstman et al. 2007b; Jacobson and Jacobson 2003), and immunosuppression (Hertz­Picciotto et al. 2008). Gestational weight gain (GWG) is itself a potential influence on the growth and health of the fetus and later outcomes during childhood and adulthood (Viswanathan et al. 2008). "
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    ABSTRACT: Exposure to persistent organic pollutants (POPs) during fetal development can increase the risk of adverse health effects during childhood. Maternal characteristics and physiological changes during gestation such as gestational weight gain (GWG) may have an influence in the overall burden of POPs in neonates. However, the associations between GWG and POP concentrations are still not well established. We examined the association of GWG with cord serum POPs concentrations after adjusting for pre-pregnancy maternal body mass index (BMI) and other potential determinants of the transfer of POPs into newborns. The GWG values were evaluated after grouping by the reference guidelines of the Institute of Medicine (IOM). We measured levels of 14 organochlorine pesticides, 7 polychlorobiphenyls (PCBs) and 14 polybromodiphenyl ethers (PBDEs) in 325 cord serum samples from a Spanish birth cohort. Multivariable models were used to estimate associations of GWG, pre-pregnancy BMI, and other maternal determinants on cord serum concentrations of POPs. Neonatal concentrations of POPs were inversely associated with GWG after adjustment for age, pre-pregnancy BMI, educational level, and fish consumption. On average, neonates of women with IOM recommended GWG have lower POP concentrations than neonates of mothers with inadequate GWG. The present findings suggest an association between neonatal exposure to POPs and inadequate GWG during pregnancy. Encouraging pregnant women to meet the recommended IOM guidelines for GWG may reduce the accumulation of POPs in newborns.
    Full-text · Article · May 2014 · Environmental Health Perspectives
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