Occurrence and Effect of environmental progesterone receptor ligands on fish reproduction and neurodevelopment – PROOFS

PROOFS is an interdisciplinary project aiming at studying the potential impact of environmental progestins on the neurodevelopment and on the reproduction in fish but also at investigating the progestative activities of environmental samples and identifying the compounds responsible these biological activities.
The rationale behind PROOFS is that, during the last two decades, a large number of studies have investigated the risk posed by natural and synthetic steroidal estrogens on aquatic organism reproductive health while virtually no study have been conducted on the potential endocrine disrupting effect of natural and synthetic progestins. This results in a significant lack of data to characterize the hazard and the risk of this class of environmental contaminant on fish reproductive health. However, there exists evidence to show that there is increasing concentrations of progestagens in the European river waters and that progestins can adversely affect the reproductive function of fish. Progesterone and synthetic progestins (used in contraceptive pills) are present in effluents as well as in surface waters (and probably sediments) at concentration that often exceed those of natural and synthetic estrogens, i.e. in the ng/L range. Second, progesterone are endogenous steroid hormones are key players of important reproductive functions in both male and female, since they are directly involved in stimulation of spermiation and sperm motility in male, in the stimulation of oocyte final maturation and ovaulation in females, and the initiation of meiosis in both sexes. It is also known that progesterone and progesterone derivatives are major neurosteroids, i.e. steroids that are produced by the brain itself. Both nuclear and membrane progesterone receptors are highly expressed in the brain, including in neuronal progenitors that sustain the growth of fish brain throughout the entire lifespan. This suggest that neuronal progenitors are targeted by endogenous progestagens and thus potentially by progestagens present in the environment.

The PROOFS consortium aims to (i) to establish new in vitro tools to assess the progestative activities of environmental samples and (ii) to better understand the effects of progestagens on neurodevelopment in zebrafish as well as to characterize their effect on fish reproduction by studying a set of known and relevant hormone-regulated genes.
The expected output are 1) the improvement of knowledge of progestins in fish and 2) a better characterization of hazard of these compounds as regards to their endocrine disrupting potency in aquatic vertebrates which is a prerequisite for future risk assessment.