E1 and E2 acted in an additive manner on cyp19a1b-driven GFP expression that was predicted by the CA model, in agreement with previous data on vitellogenin synthesis or on zebrafish cyp19a1b-luciferase activity in vitro. It highlights the interest of the tg in combination with CA models to assess combined effect of estrogenic compounds. In conclusion, the tg line clearly emerges as a simple, fast and reliable in vivo assay for monitoring the capacity of any chemical or its metabolites to activate ER-signalling in vivo at very early critical developmental stages. It is based on the use of an endogenous promoter and thus shows of a true physiological brainspecific response. Its sensitivity is outstanding and comparable to the most performing in vitro assays. In complement of the in vitro assay using the same cyp19a1b promoter, this in vivo assay will permit taking into account the biodisponility and pharmacodynamics of chemicals. This will enhance the efficiency and accuracy of EDCs testing strategies while meeting the 3R policy that is enforced by the OECD and the main environmental agencies worldwide. Finally, although the potential consequences of such exposures are unknown, the present data showing direct effects of EDCs on gene expression in radial glial progenitors raise several serious issues in the context of risk assessment. One of them is to evaluate to what extent the present findings may apply to other vertebrates. Some studies indicate that estrogens indeed affect early brain development in rodents, but there is a lack on data the expression on steroidogenic enzymes, notably aromatase, and estrogen receptors, notably ERb in the developing brain. Similarly, the roles of steroids in early aromatase expression are unknown. Additionally, the potential production and effects of beta-diol, sometimes referred to as the “second estrogen”, have just started to receive some attention, albeit the present work recalls that this alternative pathway should not be forgotten in the context of developing animals. The clinically relevant bloodstream form lives in the bloodstream and lymph of the host in the first stage of the disease, before crossing the blood-brain barrier in the second stage of the disease leading to coma and death. The pleomorphic bloodstream form exists as both a replicative PB 203580 152121-47-6 long-slender morphology and a division arrested stumpy form which is preadapted for transmission into the tsetse fly. Upon ingestion by the tsetse fly the parasite differentiates into a replicative procyclic form to enable survival in its new environment. The lifecycle is completed by migration to the salivary glands and transformation to an adherent epimastigote form, followed by transformation to a detached metacyclic form, which is then competent for transmission into the bloodstream of the mammalian host when the tsetse takes a blood-meal. Both the procyclic form and bloodstream form of the parasite may be cultured in vitro. To drive expression of the selectable marker and test gene respectively. Through adaptation to continuous culture the bloodstream form parasite has become monomorphic, having lost the ability to spontaneously transform to stumpy morphology, but is still considered a relevant model system. Trypanosomes are one of the most evolutionarily divergent eukaryotes for which there are molecular data. The regulation of gene expression in trypanosomes is distinct from that in most euk

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