RESUMO
Lead is a widely used heavy metal that can affect children's nervous system development. ALAD gene polymorphism is associated with lead neurotoxicity. This study aimed to clarify the relationship among maternal blood lead, ALAD gene polymorphism, and neonatal neurobehavioral development through detecting maternal blood lead and ALAD gene polymorphism. 198 maternal and neonatal were selected as the research object. Graphite furnace atomic absorption method was applied to detect the maternal blood lead concentration. PCR-RFLP was used to detect ALAD genotype distribution. Neonatal NANB score was treated as effect indicator. SPSS was used for statistical analysis. The ALAD genotype was 181 cases (91.4%) for ALAD11 and 17 cases (8.6%) for ALAD12. ALAD allele frequency distribution accords with genetics Hardy-Weinberg balance (P > 0.05). Blood lead level in maternal with ALAD12 genotype was significantly higher than with ALAD11 genotype (P < 0.01). NANB score in high blood lead neonatal group was obviously lower than the low blood lead group (P < 0.05). Newborn's NANB score from the maternal with ALAD11 genotype was lower than from the maternal with ALAD12 genotype (P < 0.01). After ruling out the confounding factors influence by multiple linear regressions, ALAD gene polymorphisms had no significant correlation with neonatal NANB score (P > 0.05). ALAD gene polymorphism is associated with the blood lead level. Low level lead exposure in utero may cause newborn early neurobehavioral maldevelopment. Maternal ALAD gene polymorphism can affect early neonatal neurobehavioral development by influencing the blood lead level.
Assuntos
Desenvolvimento Infantil/efeitos dos fármacos , Deficiências do Desenvolvimento/genética , Intoxicação do Sistema Nervoso por Chumbo na Infância/genética , Chumbo/sangue , Exposição Materna , Troca Materno-Fetal , Polimorfismo Genético , Sintase do Porfobilinogênio/genética , Efeitos Tardios da Exposição Pré-Natal , Adulto , Fatores Etários , Deficiências do Desenvolvimento/sangue , Deficiências do Desenvolvimento/diagnóstico , Deficiências do Desenvolvimento/enzimologia , Feminino , Predisposição Genética para Doença , Humanos , Recém-Nascido , Chumbo/efeitos adversos , Intoxicação do Sistema Nervoso por Chumbo na Infância/sangue , Intoxicação do Sistema Nervoso por Chumbo na Infância/diagnóstico , Intoxicação do Sistema Nervoso por Chumbo na Infância/enzimologia , Modelos Lineares , Fenótipo , Sintase do Porfobilinogênio/metabolismo , Gravidez , Fatores de Risco , Espectrofotometria AtômicaAssuntos
Encéfalo/enzimologia , Cerebrosídeo Sulfatase/metabolismo , Intoxicação do Sistema Nervoso por Chumbo na Infância/enzimologia , Células-Tronco Neurais/enzimologia , Neurogênese , Oligodendroglia/enzimologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Encéfalo/fisiopatologia , Cerebrosídeo Sulfatase/genética , Modelos Animais de Doenças , Predisposição Genética para Doença , Humanos , Intoxicação do Sistema Nervoso por Chumbo na Infância/genética , Intoxicação do Sistema Nervoso por Chumbo na Infância/patologia , Intoxicação do Sistema Nervoso por Chumbo na Infância/fisiopatologia , Intoxicação do Sistema Nervoso por Chumbo na Infância/psicologia , Aprendizagem , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/patologia , Neurogênese/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/patologia , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/patologia , Fenótipo , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Transdução de SinaisRESUMO
Developmental exposure to lead (Pb) has adverse effects on cognitive functioning and behavior that can persist into adulthood. Exposures that occur during fetal or early life periods may produce changes in brain related to physiological re-programming from an epigenetic influence such as altered DNA methylation status. Since DNA methylation is regulated by DNA methyltransferases and methyl cytosine-binding proteins, this study assessed the extent to which developmental Pb exposure might affect expression of these proteins in the hippocampus. Long Evans dams were fed chow with or without added Pb acetate (0, 150, 375, 750 ppm) prior to breeding and remained on the same diet through weaning (perinatal exposure group). Other animals were exposed to the same doses of Pb but exposure started on postnatal day 1 and continued through weaning (early postnatal exposure group). All animals were euthanized on day 55 and hippocampi were removed. Western blot analyses showed significant effects of Pb exposure on DNMT1, DNMT3a, and MeCP2 expression, with effects often seen at the lowest level of exposure and modified by sex and developmental window of Pb exposure. These data suggest potential epigenetic effects of developmental Pb exposure on DNA methylation mediated at least in part through dysregulation of methyltransferases.
