In the first phase of FREIA, the “Discovery phase”, we looked for biological characteristics (biomarkers) that can be linked to female reproductive toxicity and test methods to measure this. For this, we use two well-understood EDCs: diethylstilbestrol (DES, a potent oestrogen receptor activator) and ketoconazole (a blocker of steroid hormone production).
Next, we will assess how well our test methods and potential novel endpoints can identify EDCs that cause female reproductive toxicity.
Here, we briefly describe the main findings from the first 36 months of the FREIA project, from January 2019 until December 2021. The full summary of the first and second periodic report that were submitted to the European Commission can be downloaded below.
HIGHLIGHTS OF MAIN RESULTS SO FAR
Exposure to ketoconazole diminishes the number of immature oocytes in cultivated human embryonic ovaries.
From women undergoing fertility treatment, fewer oocytes could be retrieved when levels of some EDCs were higher in the biological fluids surrounding the oocytes.
Female rats that were exposed to DES or ketoconazole in the womb started puberty at a later age than female rats that were not exposed. The hormone release in the brain of these animals was also delayed. Interestingly, fewer animals are needed to see this effect in the brain, which may reduce the need for test animals in the future.
Several cell models and computer models have been developed or improved. We focus on ovarian cells and targets that are involved in female reproductive health, such as the oestrogen receptor (target for oestrogen) and aromatase enzyme (involved in oestrogen production).
We have constructed sixteen possible pathways to explain how EDCs can cause female reproductive disorders. This will help us to pinpoint which test methods are needed to predict a chemical’s effect on female reproductive health.
TOWARDS OUR MAIN GOAL
The FREIA project aims to provide better test methods to identify human-made chemicals that disturb hormones and their actions on development and function of the reproductive system in women.
We have already found some clear effects of EDCs on oocytes and hormonal processes that are linked to female reproductive health. These findings may pinpoint relevant test methods to support identification of EDCs that are harmful to female reproductive health.