Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Transcription profiling of chord and interstitial regions of rat testes at gestational day 19 treated in utero with dibutylphthalate (DBP)

ABSTRACT: An experiment was performed to assess the effects on rats of in utero dibutylphthalate (DBP)-treatment on the transcriptome of whole fetal testes at gestational day 19.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Simon plummer

PROVIDER: E-TABM-201 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Time-dependent and compartment-specific effects of in utero exposure to Di(n-butyl) phthalate on gene/protein expression in the fetal rat testis as revealed by transcription profiling and laser capture microdissection.

Plummer Simon S Sharpe Richard M RM Hallmark Nina N Mahood Isobel Kim IK Elcombe Cliff C

Toxicological sciences : an official journal of the Society of Toxicology 20070322 2

We undertook transcription profiling of fetal testis RNA on gestational days e15.5, 17.5, and 19.5 in offspring from dams treated daily from e12.5 with 500 mg/kg di(n-butyl) phthalate (DBP). At e17.5-19.5, reduced expression of genes involved in cholesterol uptake/metabolism and steroidogenesis was identified in DBP-exposed animals, including scavenger receptor B1 (SCARB1), HMGCoA synthase, steroidogenic acute regulatory protein, Cyp11a, and Cyp17. Genes encoding inhibin-alpha, phosphatidylethan ...[more]

PMID: 17379624

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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.

Dataset Information

Transcription profiling of chord and interstitial regions of rat testes at gestational day 19 treated in utero with dibutylphthalate (DBP)

Publications

Time-dependent and compartment-specific effects of in utero exposure to Di(n-butyl) phthalate on gene/protein expression in the fetal rat testis as revealed by transcription profiling and laser capture microdissection.

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