Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol
This study examined the effects of estrogen receptor agonist, ethinylestradiol, and the phospholipase A2 inhibitor, quinacrine, on the pathways controlling follicular recruitment, steroidogenesis, oocyte maturation and ovulation and spawning success in the adult zebrafish. Ethinylestradiol and quinacrine both inhibit spawning but did so through different adverse outcome pathways. Ethinylestradiol affected follicular recruitment (reduced ovarian size and reduction in the proportion of cortical alveolus, vitellogenic and mature follicle stages), steroidogenesis (reduced expression of aromatase) maturation (reduced luteinizing hormone receptor expression) and ovulation (reduced expression of cytosolic phospholipase A2 and the nuclear progesterone receptor). Quinacrine targeted ovulation via a reduction of the steroid 17α, 20β dihydroxy-4-prenen-3-one and expression of the prostaglandin metabolizing enzyme cyclooxygenase 2. Collectively, these studies suggest that a targeted assessment of reproductive endpoints can be used effectively to identify the adverse outcome pathways by which toxicants can impact reproductive fitness.