Sex-based differences in gene expression in hippocampus following postnatal lead exposure

Abstract

The influence of sex as an effect modifier of childhood lead poisoning has received little systematic attention. Considering the paucity of information available concerning the interactive effects of lead and sex on the brain, the current study examined the interactive effects of lead and sex on gene expression patterns in the hippocampus, a structure involved in learning and memory. Male or female rats were fed either 1500 ppm lead-containing chow or control chow for 30 days beginning at weaning. Blood lead levels were 26.7 ± 2.1 μg/dl and 27.1 ± 1.7 μg/dl for females and males, respectively. The expression of 175 unique genes was differentially regulated between control male and female rats. A total of 167 unique genes were differentially expressed in response to lead in either males or females. Lead exposure had a significant effect without a significant difference between male and female responses in 77 of these genes. In another set of 71 genes, there were significant differences in male vs. female response. A third set of 30 genes was differentially expressed in opposite directions in males vs. females, with the majority of genes expressed at a lower level in females than in males. Highly differentially expressed genes in males and females following lead exposure were associated with diverse biological pathways and functions. These results show that a brief exposure to lead produced significant changes in expression a variety of genes in the hippocampus and that the response of the brain to a given lead exposure may vary depending on sex.

Effects of low level lead exposure on associative learning and memory in the rat: Influences of sex and developmental timing of exposure

“…We and others have previously reported sex-related differences in hippocampus-based learning and memory (Anderson et al, 2012), gene expression patterns in both the frontal cortex and hippocampus of littermates (Anderson et al, 2013; Schneider et al, 2011) and modulation of epigenetic control elements including DNA methyltransferases of littermates (Schneider et al, 2013) following Pb-exposure. The results of the current study suggest that there are also complex effects of sex, developmental window of exposure and level of Pb-exposure on associative memory as assessed by trace fear conditioning.…”

Sex- and tissue-specific methylome changes in brains of mice perinatally exposed to lead

“…Brain differences between males and females are a common phenomenon, since sexual differentiation in the brain takes place during a perinatal sensitive window as a result of gonadal hormone-induced developmental organization (Auger and Auger 2013; Chung and Auger 2013; Menger et al 2010). Sex differences in gene expression patterns and in the regulation of genes coding for DNA methylases have been observed in hippocampus and frontal cortex of rats exposed to lead (Schneider et al 2011; Schneider et al 2012b), and shown to be differentially expressed depending on the developmental timing of the exposure (Schneider et al 2012a). The effect of sex in the regulation of the genome and epigenome is largely unexplored.…”

Influence of developmental lead exposure on expression of DNA methyltransferases and methyl cytosine-binding proteins in hippocampus

“…Although the reasons for this sex-related difference in response to Pb are not entirely clear, sex differences in the response to Pb have been reported in other contexts (Cory-Slechta et al, 2004). Sex-related differences in gene expression patterns have been observed in hippocampus (Schneider et al, 2011) and frontal cortex (Schneider et al, 2012b) and in the expression of learning and memory deficits in Pb-exposed animals (Anderson et al, 2012), and these effects are expressed differently depending on the developmental period of Pb exposure (Anderson et al, 2012; Schneider et al, 2012a). Little is known in general regarding sex differences in the regulation of the genome and epigenome.…”