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Microarray analysis of MEHP gavaged PND28 male rats

ABSTRACT: In rodent models, phthalate exposure alters both the fetal and pubertal testis, but the resulting histopathological changes are divergent. This suggests that the underlying molecular and cellular phthalate mechanism may be age-dependent. Using genome-wide expression profiling of acutely-exposed rats, the initial molecular response in pubertal rat testis following in vivo phthalate exposure was determined. For this study, postnatal day 28 rats were exposed to a single dose of 1 g/kg mono-(2-ethyl)hexyl phthalate (MEHP) and assayed at 1, 2, 3, 6, and 12 hrs thereafter using Affymetrix Rat Genome 230 2.0 Arrays. Keywords: Time course, single dose

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE4514 | GEO | 2006/04/01

SECONDARY ACCESSION(S): PRJNA94519

REPOSITORIES: GEO

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Project description:The purpose of this study is to assess the potential of TOTM to induce testicular maldevelopment in the rat. We studied the effects of TOTM on the expression of genes in pathways involved in steriodogenesis and testes development. Certain phthalate esters have previously been shown to be involved in the induction of rat testicular mal-development (TMD) through effects on the expression of genes in pathways involved in steroidogenesis and testes development. In order to assess the effects of a potential alternate plasticizer, tris(2-ethylhexyl)trimellitate (TOTM), rats were exposed daily, in utero, to TOTM in order to assess the potential of this compound to induce developmental effects on the fetal testes. Pregnant rats were exposed between gestational day 12 and 19 and fetal testes RNA was analysed using whole genome microarrays. The effects of TOTM on the expression of genes in pathways involved in steroidogenesis and testes development were examined. The effects of TOTM were also compared with di(2-ethylhexyl)phthalate (DEHP), mono(2-ethylhexyl)phthalate (MEHP), an active metabolite of DEHP, and 2-ethylhexanol (2-EH), which were used as positive and negative controls, respectively. MEHP & DEHP (500mg/kg) caused a repression of genes in TMD pathways involved in cholesterol synthesis and transport (HMGCS, HMGCR, StAR, SCARB1, FDFT1, FDPS), steroidogenesis (Cyp11a, HSD3B1, SC4MOL) and testes development (INSL3, INHA). 2-EH caused minor repression of some of the genes in the TMD pathway. This was rationalised on the basis that 2-EH, a DEHP metabolite, is also a weak PPARα agonist. It has been shown that in utero treatment with DBP will repress the genes from fetal testes involved in steroidogenesis and that this effect is associated with direct DBP-mediated binding of PPARα to the promoters of these genes (Plummer et. al. 2010). TOTM did not cause a significant repression of genes in the TMD pathway. Based on these data, it is highly unlikely that TOTM will cause testicular dysgenesis in rats. Rats were exposed to TOTM in utero by the administration of daily oral gavage doses to pregnant dams between gestational day 12 and 19. The foetal testes were obtained by micro-dissection and prepared to facilitate the isolation of RNA, which was subsequently analysed using whole rat genome microarrays.

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Microarray analysis of MEHP gavaged PND28 male rats

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