Neurodevelopmental effects of natural and synthetic ligands of estrogen and progesterone receptors in zebrafish eleutheroembryos

•Estradiol, progesterone and norethindrone, a 19-nortestosterone synthetic progestin with estrogenic properties, affect brain expression of estrogen and progesterone nuclear receptors in zebrafish larvae.•Progesterone inhibits the proliferation in the brain of zebrafish larvae.•Estradiol inhibits the proliferation in the brain of zebrafish larvae.•Norethindrone increases the number of apoptotic cells in the brain of zebrafish larvae.•The effects induced by the three steroids on zebrafish brain development were clearly different. Natural and synthetic estrogens and progestins are widely used in human and veterinary medicine and are detected in waste and surface waters. Our previous studies have clearly shown that a number of these substances targets the brain to induce the estrogen-regulated brain aromatase expression but the consequences on brain development remain virtually unexplored. The aim of the present study was therefore to investigate the effect of estradiol (E2), progesterone (P4) and norethindrone (NOR), a 19-nortestosterone progestin, on zebrafish larval neurogenesis. We first demonstrated using real-time quantitative PCR that nuclear estrogen and progesterone receptor brain expression is impacted by E2, P4 and NOR. We brought evidence that brain proliferative and apoptotic activities were differentially affected depending on the steroidal hormone studied, the concentration of steroids and the region investigated. Our findings demonstrate for the first time that steroid compounds released in aquatic environment have the capacity to disrupt key cellular events involved in brain development in zebrafish embryos further questioning the short- and long-term consequences of this disruption on the physiology and behavior of organisms.