Gene expression in the mouse brain following early pregnancy exposure to ethanol

Abstract

Exposure to alcohol during early embryonic or fetal development has been linked with a variety of adverse outcomes, the most common of which are structural and functional abnormalities of the central nervous system [1]. Behavioural and cognitive deficits reported in individuals exposed to alcohol in utero include intellectual impairment, learning and memory difficulties, diminished executive functioning, attention problems, poor motor function and hyperactivity [2]. The economic and social costs of these outcomes are substantial and profound [3], [4]. Improvement of neurobehavioural outcomes following prenatal alcohol exposure requires greater understanding of the mechanisms of alcohol-induced damage to the brain. Here we use a mouse model of relatively moderate ethanol exposure early in pregnancy and profile gene expression in the hippocampus and caudate putamen of adult male offspring. The effects of offspring sex and age on ethanol-sensitive hippocampal gene expression were also examined. All array data are available at the Gene Expression Omnibus (GEO) repository under accession number GSE87736.

Murine sperm capacitation, oocyte penetration and decondensation following moderate alcohol intake

“…One important feature of the present ethanol intake model in drinking water is that CF-1 mice reliably drank ethanol to moderate BAC levels (range 15-60 mg/dL) and consumed 30 g ethanol/ kg body weight daily, similar to other paradigms of ethanol drinking intake with 10, 20 or 30% ethanol that produce an average BAC of approximately 1.6 mg/mL (Rhodes et al 2005). With this value of moderate BAC levels, we found changes in fertilization outcome even though other authors did not find effects on reproductive parameters (Ogilvie et al 1997, Bonthius et al 2002, Zhang & Chong 2016. Furthermore, although the value of 30.3% EDC obtained was relatively low compared to value ranges previously reported (Willis et al 1983, Abel & Moore 1987, Shirai & Ikemoto 1992, Mittleman et al 2003, we observed not only an effect on fertilization but also altered sperm morphology and capacitation parameters.…”

Neurological and neuropsychological effects of low and moderate prenatal alcohol exposure

“…Four genes were found to be differently expressed (Inmt, Mia1, Slc17a6, Tshz2) in the hippocampus of adult male offspring of pregnant mice drinking 10% ethanol during E0-E8 with blood alcohol concentration (BAC) 26 mmol L À1 , 120 mg dL À1 , where in particular the expression of the glutamate transporter Slc17a6 was confirmed to be increased. 50 Altered expression of c-fos and Arc genes were found in several different regions of the frontal cortex of rat offspring exposed to ethanol during pregnancy (BEC 18 mmol L À1 , 83 mg dL À1 ) compared with expression patterns in non-ethanol-exposed controls. 51,52 Recently, ethanol-induced epigenetic effects have also been reported in experimental models.…”

“…Radial glial cells expressing vimentin, nestin, S‐100b and Pax6 displayed abnormal morphology, and the number of doublecortin‐ir neuroblasts in germinative zones was decreased, all of which may contribute to cortical dysplasia in prenatally ethanol‐exposed offspring. Four genes were found to be differently expressed ( Inmt, Mia1, Slc17a6, Tshz2) in the hippocampus of adult male offspring of pregnant mice drinking 10% ethanol during E0–E8 with blood alcohol concentration (BAC) 26 mmol L −1 , 120 mg dL −1 , where in particular the expression of the glutamate transporter Slc17a6 was confirmed to be increased . Altered expression of c‐fos and Arc genes were found in several different regions of the frontal cortex of rat offspring exposed to ethanol during pregnancy (BEC 18 mmol L −1 , 83 mg dL −1 ) compared with expression patterns in non‐ethanol‐exposed controls …”

Pre-implantation alcohol exposure and developmental programming of FASD: an epigenetic perspective

“…GD0.5 to GD8.5 10% EtOH Voluntary drinking Mouse P87 Hippocampus ↑ SLC17a6 expression (Zhang and Chong 2016) All gestation and 10 days after (Allan et al 2003) GD1 to GD22 4.5g/kg Gavage Rat P21 Hippocampus ↑ DNMTs acƟvity Gene expression changes in Dnmt1, Dnmt3a and MeCP2 (Perkins et al 2013) GD1 to GD16 4% EtOH Liquid diet Mouse GD17, P7…”