Staff Publications

Staff Publications

  • external user (warningwarning)
  • Log in as
  • language uk
  • About

    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

    We have a manual that explains all the features 

Record number 439734
Title Toxicogenomics-based in vitro alternatives for estrogenicity testing
Author(s) Wang, S.
Source Wageningen University. Promotor(en): Ivonne Rietjens, co-promotor(en): Toine Bovee; Jac Aarts. - S.l. : s.n. - ISBN 9789461735812 - 193
Department(s) Sub-department of Toxicology
RIKILT - BU Toxicology Bioassays & Novel Foods
Publication type Dissertation, internally prepared
Publication year 2013
Keyword(s) oestrogene eigenschappen - oestrogenen - in vitro - toxicogenomica - testprocedure - alternatieve methoden - methodologie - oestrogenic properties - oestrogens - toxicogenomics - test procedure - alternative methods - methodology
Categories Toxicology (General)

Testing chemicals for their endocrine-disrupting potential, including interference with estrogen receptor signaling, is an important aspect to assess the safety of currently used and newly developed chemicals. The standard test for disruption of normal estrogen function is the in vivo uterotrophic assay in immature or ovariectomised rodents with uterus weight as a crucial read-out parameter. Due to the high costs, ethical objections and labour intensiveness of the in vivo uterotrophic assay, the development of an in vitro test battery for in vivo estrogenicity has high priority. The aim of the present thesis was to develop an integrated testing strategy (ITS), based on existing and newly developed in vitro assays for estrogenicity testing, allowing easy high-throughput screening and prioritization of chemicals. An ITS preferentially based on in vitro assays would be a crucial step towards refinement, reduction, and ultimately replacement of current animal testing for estrogenic and other endocrine disrupting effects.

To reach this aim, several presently available and newly developed in vitro bioassays were selected and evaluated for optimal representation of the estrogenic effects occurring in the uterus/endometrium in vivo. Results show that the yeast estrogen bioassay revealed the best correlation with the in vivo uterotrophic assay(R2=0.87). The estrogenic potencies predicted by the peptide microarray also correlated very well with the uterotrophic assay and 30 coactivators on the peptide microarray resulted in correlation coefficient values higher than 0.85. The present thesis thus provides proof-of-principle that combining in vitro assays measuring different steps in the estrogen receptor signaling pathway enables accurate prediction of the estrogenic effects in vivo. By including the androgen reporter gene assays as well as the H295R steroidogenesis assay, the extended testing panel even goes beyond estrogenicity testing, as it can detect possible (anti)androgenic effects and effects on steroidogenesis that are not covered by the in vivo uterotrophic assay. The integrated in vitro testing strategy presented in this thesis may therefore allow easy high-throughput screening and prioritization of chemicals, thereby contributing to refinement, reduction and to some extent even replacement of current animal testing for estrogenic effects.

There are no comments yet. You can post the first one!
Post a comment
Please log in to use this service. Login as Wageningen University & Research user or guest user in upper right hand corner of this page.