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

Abstract

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 longterm consequences of this disruption on the physiology and behavior of organisms.

Post-Traumatic Expressions of Aromatase B, Glutamine Synthetase, and Cystathionine-Beta-Synthase in the Cerebellum of Juvenile Chum Salmon, Oncorhynchus keta

“…The detection of aromatase B activity in these cell types may be related to their estrogenic modulation. In particular, the processes of the growth, differentiation, and migration of cells during constitutive neurogenesis can be regulated by estrogens, which is consistent with data on other species [41,43,71,72].…”

Zebrafish as an emerging model to study estrogen receptors in neural development

“…Moreover, 17β-estradiol treatment led to a significant decrease in PCNA positive cells, suggesting a role for estrogens in inhibiting cell proliferation through their nuclear receptors, at least partially, in adult zebrafish brain ( 44 , 68 – 70 ). As for embryonic studies, treating zebrafish embryos with E2, during nervous system development, decreased the number of BrdU positive cells in the thalamus, olfactory bulbs, telencephalon and preoptic areas, while no difference was observed in mediobasal and caudal hypothalamus ( 71 ). Even though some of the areas affected differ between zebrafish adults and larvae, a clear inhibitory effect of estradiol on proliferative activity of neural cells is observed in zebrafish ( 69 , 71 ).…”

“…As for embryonic studies, treating zebrafish embryos with E2, during nervous system development, decreased the number of BrdU positive cells in the thalamus, olfactory bulbs, telencephalon and preoptic areas, while no difference was observed in mediobasal and caudal hypothalamus ( 71 ). Even though some of the areas affected differ between zebrafish adults and larvae, a clear inhibitory effect of estradiol on proliferative activity of neural cells is observed in zebrafish ( 69 , 71 ). Several studies highlighted a potential role for aromatase in RG development, given its high expression in RGs.…”