Endocrine disruptors and childhood social impairment

Department of Preventive Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
NeuroToxicology (Impact Factor: 3.38). 12/2010; 32(2):261-7. DOI: 10.1016/j.neuro.2010.12.009
Source: PubMed


Prenatal exposure to endocrine disruptors has the potential to impact early brain development. Neurodevelopmental toxicity in utero may manifest as psychosocial deficits later in childhood. This study investigates prenatal exposure to two ubiquitous endocrine disruptors, the phthalate esters and bisphenol A (BPA), and social behavior in a sample of adolescent inner-city children. Third trimester urines of women enrolled in the Mount Sinai Children's Environmental Health Study between 1998 and 2002 (n=404) were analyzed for phthalate metabolites and BPA. Mother-child pairs were asked to return for a follow-up assessment when the child was between the ages of 7 and 9 years. At this visit, mothers completed the Social Responsiveness Scale (SRS) (n=137), a quantitative scale for measuring the severity of social impairment related to Autistic Spectrum Disorders (ASD) in the general population. In adjusted general linear models increasing log-transformed low molecular weight (LMW) phthalate metabolite concentrations were associated with greater social deficits (β=1.53, 95% CI 0.25-2.8). Among the subscales, LMWP were also associated with poorer Social Cognition (β=1.40, 95% CI 0.1-2.7); Social Communication (β=1.86, 95% CI 0.5-3.2); and Social Awareness (β=1.25, 95% CI 0.1-2.4), but not for Autistic Mannerisms or Social Motivation. No significant association with BPA was found (β=1.18, 95% CI -0.75, 3.11). Prenatal phthalate exposure was associated with childhood social impairment in a multiethnic urban population. Even mild degrees of impaired social functioning in otherwise healthy individuals can have very important adverse effects over a child's lifetime. These results extend our previous finding of atypical neonatal and early childhood behaviors in relation to prenatal phthalate exposure.

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    • "Experiments in cell culture systems have shown that EDCs such as bisphenol A (BPA) and phthalates alter the growth of neuronal processes and the formation of synapses (Yokosuka et al. 2008; Matsunaga et al. 2010; Xu et al. 2014). It has also been found that prenatal exposure to EDCs is associated with atypical neurological function and behaviour in infants and children (Braun et al. 2009; Engel et al. 2009; Miodovnik et al. 2011; Harley et al. 2013). "
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    ABSTRACT: Cultures of dissociated hippocampal neurons are often used to study neuronal cell biology. We report that the development of these neurons is strongly affected by chemicals leaching from commonly used disposable medical-grade syringes and syringe filters. Contamination of culture medium by bioactive substance(s) from syringes and filters occurred with multiple manufacturing lots and filter types under normal use conditions and resulted in changes to neurite growth, axon formation and the neuronal microtubule cytoskeleton. The effects on neuronal morphology were concentration-dependent and significant effects were detected even after substantial dilution of the contaminated medium. Gas chromatography-mass spectrometry (GC-MS) analyses revealed many chemicals eluting from the syringes and filters. Three of these chemicals (stearic acid, palmitic acid and 1,2-ethanediol monoacetate) were tested but showed no effects on neurite growth. Similar changes in neuronal morphology were seen with high concentrations of bisphenol A (BPA) and dibutyl phthalate (DBP), two hormonally-active plasticisers. Although no such compounds were detected by GC-MS, unknown plasticisers in leachates may affect neurites. This is the first study to show that leachates from laboratory consumables can alter the growth of cultured hippocampal neurons. We highlight important considerations to ensure leachate contamination does not compromise cell biology experiments.This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2014 · Journal of Neurochemistry
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    • "There is a growing literature that suggests that early exposure to environmental contaminants, specifically those with endocrine-disrupting properties, may be associated with an increased risk of neurological disorders, such as autism. Examples include studies investigating early exposure to phthalates, polybrominated diphenyl ethers, and polychlorinated biphenyls (Larsson et al., 2009; Miodovnik et al., 2011; Mitchell et al., 2012; Testa et al., 2012; Woods et al., 2012). Although the magnitude seen in the present study is relatively small, there is evidence that large increases in neurons and glia are found in human males diagnosed with autism (Courchesne et al., 2011; Edmonson et al., 2014). "
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    ABSTRACT: Previous work has shown that exposure to bisphenol A (BPA) during early development can alter sexual differentiation of the brain in rodents, although few studies have examined effects on areas of the brain associated with cognition. The current study examined if developmental BPA exposure alters the total number of neurons and glia in the medial prefrontal cortex (mPFC) in adulthood. Pregnant Long-Evans rats were orally exposed to 0, 4, 40, or 400 μg/kg BPA in corn oil throughout pregnancy. From postnatal days 1-9, pups were given daily oral doses of oil or BPA, at doses corresponding to those given during gestation. Brains were examined in adulthood, and the volume of layers 2/3 and layers 5/6 of the mPFC were parcellated. The density of neurons and glia in these layers was quantified stereologically with the optical disector, and density was multiplied by volume for each animal. Males exposed to 400 μg/kg BPA were found to have increased numbers of neurons and glia in layers 5/6. Although there were no significant effects of BPA in layers 2/3, the pattern of increased neuron number in males exposed to 400 μg/kg BPA was similar to that seen in layers 5/6. No effects of BPA were seen in females or in males exposed to the other doses of BPA. This study indicates that males are more susceptible to the long-lasting effects of BPA on anatomy of the mPFC, an area implicated in neurological disorders.
    Full-text · Article · Sep 2014 · Neuroscience
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    • "While the size of our study (148 mother–child pairs) did not allow for separate analyses for males and females, several studies have suggested an infant sex modified association between phthalates and developmental scores [13] [15] [16]. No sex-specific differences were observed in the association between prenatal phthalate exposure and childhood social impairment at 7–9 years of age [14]. Further analyses to examine differences in neurodevelopmental effects of phthalates between males and females seem reasonable and could be performed for the REPRO_PL cohort in the future. "
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    ABSTRACT: Background Widespread phthalate exposure has prompted investigations concerning their potential adverse health effects. The objective of this study was to evaluate the impact of pre and early postnatal phthalate exposure on child psychomotor development basing on the data from the prospective Polish Mother and Child Cohort Study (REPRO PL). Methods Phthalate exposure was determined by measuring 11 phthalate metabolites (MEP, MiBP, MnBP, 3OH-MnBP, MBzP, MEHP, 5OH-MEHP, 5oxo-MEHP, 7OH-MiNP, 7oxo-MiNP, MnOP) in the urine collected from mothers during the third trimester of pregnancy (prenatal exposure) and from their children at 24 th month of age (postnatal exposure). The analysis was performed by HPLC-MS/MS method. Child psychomotor development was assessed at the 2 nd year of age by Bayley Scales of Infant and Toddler Development. Results Child motor development was inversely associated with natural log concentrations (µg/g creatinine) of 3OH-MnBP (β=-2.3; 95% CI -4.0 to -0.6), 5OH-MEHP (β=-1.2; 95% CI -2.2 to -0.3), 5oxo-MEHP (β=-1.8; 95% CI -330 to -0.2) and DEHP metabolites (β=-2.2; 95% CI -3.60 to -0.8) and sum of high molecular weight phthalates (β=-2.5; 95% CI -4.1 to -0.9) in the urine collected from mothers during pregnancy after adjustment for variety of potential confounders. Additional adjustment for postnatal phthalate exposure did not change the results. Postnatal child exposure to phthalates was not associated with any of the measured scores of child psychomotor development. Conclusions The study findings add further support to the possibility that prenatal phthalate exposure may be detrimental to child neurodevelopment and underscore the importance of policies and public health interventions to reduce such exposure.
    Full-text · Article · Sep 2014 · Early Human Development
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