| lühikokkuvõte: |
The FREIA consortium aims to close gaps in scientific knowledge on the mechanisms by which EDCs can affect female reproduction during specific life stages and will provide test methods to address this. The FREIA consortium has human tissue models that span the entire life cycle from fetal ovarian and adrenal tissues to child and mature ovarian follicles, that will be used identify human relevant biomarkers of EDC exposure. We will measure chemical exposures in follicular fluids and molecular profiles in granulosa cells from two IVF cohorts, and link these to fertility outcomes and patient journal information, including life-style factors and workplace. We will perform in vivo rodent studies to capture susceptible windows of exposure and identify novel endpoints for female reproductive toxicity that may be implemented in OECD test guidelines. We will provide in vitro test methods, according to OECD guidelines, for molecular and cellular events that have been implicated in female reproductive toxicity. These include ER-beta activity, GPER activity, ovarian-specific steroidogenesis, oocyte maturation and competency and hypothalamic pulsatile GnRH secretion. We will also develop QSAR models to predict interaction with aromatase and PPAR-gamma. By integrating our data from in vitro studies with primary human tissues, human exposure data from fetal and follicular fluid samples and our in vitro and in vivo research findings, the outcomes of FREIA are directly applicable to the human situation. AOPs will be developed that will form the basis for a test strategy to assess female reproductive toxicity upon exposure to EDCs, in a regulatory context. Furthermore, by expanding our scientific knowledge, the FREIA project will provide better information on EDC-related female reproductive health effects that will be used to improve reproductive health for women around the world. |
