Effects of different endocrine disruptor (EDC) mixtures on gene expression in neonatal rat brain regions: Focus on developing excitatory synapses

Walter Lichtensteiger, Catherine Bassetti-Gaille, Oliver Faass, Julie Boberg, Sofie Christiansen, Ulla Hass, Andreas Kortenkamp, Margret Schlumpf

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Sexual brain differentiation is a potential EDC target. It depends on a combination of estrogen receptor- and androgen receptor-mediated effects in males and on estrogens in females. It is not known how these processes are affected by real-world mixtures of EDCs. We investigated the effect of three EDC mixtures on gene expression in developing brain. Amix (8 anti-androgenic chemicals), Emix (4 estrogenic chemicals) and Tmix (Amix + Emix + paracetamol recently identified as anti-androgenic) were administered by oral gavage to rat dams from gestational day 7 until weaning, at doses corresponding to 450×, 200× and 100× high end human intakes (S. Christiansen et al., 2012. International Journal of Andrology 35, 303). At postnatal day 6, during the last part of sexual brain differentiation, exon microarray analyses were performed in medial preoptic area (MPO) in the highest dose group, and real time RT PCR of selected mRNA species in MPO and ventromedial hypothalamus (VMH) of all dose groups. Microarray analyses revealed mixture- and sex-specific effects on gene expression patterns. The majority of genes affected by an individual mixture was selective for that mixture. Real time RT PCR of individual mRNAs demonstrated treatment- and sex-dependent differences between MPO and VMH. Effects were dose-dependent. Prominent are effects on the expression of genes involved in excitatory glutamatergic synapse formation and function. These data indicate that effects of complex EDC mixtures on developing brain can be characterized by mixture-, sex- and region-specific gene expression patterns. Excitatory synapse development emerged as a potentially relevant target.
Original languageEnglish
JournalToxicology Letters
Issue numberSupplement
Pages (from-to)106-106
Publication statusPublished - 2013
Event49th Congress of the European Societies of Toxicology (EUROTOX) - Interlaken, Switzerland
Duration: 1 Sep 20134 Sep 2013
Conference number: 49


Conference49th Congress of the European Societies of Toxicology (EUROTOX)


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