Inhibition of spawning in zebrafish (Danio rerio): Adverse outcome pathways of quinacrine and ethinylestradiol

Abstract

INHIBITION OF SPAWNING IN ZEBRAFISH (Danio rerio): ADVERSE OUTCOME PATHWAYS OF QUINACRINE AND ETHINYLESTRADIOL Madelyne CosmeAdvisor: University of Guelph, 2014Professor. Glen Van Der KraakThis study examined the effects of estrogen receptor agonist, ethinylestradiol, and the phospholipase A 2 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.iii ACKNOWLEDGEMENTS

In vivo exposure to pyriproxyfen causes ovarian oxidative stress and inhibits follicle maturation in zebrafish

“…Our study showed that exposure to PPF causes an imbalance in the proportion of different follicular stages, with an increase in the rate of early stages, that is, follicles with previtelogenic oocytes, and diminished rate and area at later stages, namely follicles with vitellogenic oocytes. Inhibition of oocyte maturation is reported in zebrafish on exposure to following xenoestrogens such as bisphenol A (Yön & Akbulut, 2014), ethinylestradiol (Cosme et al, 2015) and phthalate (Godoi et al, 2021; Santangeli et al, 2017). Cosme et al (2015) reported that ethinylestradiol, an estrogen‐like compound, may act by inhibiting the production of LH, thus preventing the production of maturation‐inducing steroid (DHP) by follicular cells and, thus, inhibiting follicular maturation.…”

Mummichog (Fundulus heteroclitus) are less sensitive to 17α-ethinylestradiol (EE2) than other common model teleosts: A comparative review of reproductive effects

“…Alteration of aromatase expression can disrupt the rate of estrogen production, impacting local and peripheral levels of estrogens within teleosts (Cheshenko et al, 2008), and cyp19a1 is commonly used as a biomarker for estrogenic exposure (Urbatzka et al, 2012). Expression patterns of cyp19a1 are altered after exposure to EE 2 in zebrafish (Urbatzka et al, 2012;Cosme et al, 2015;Liang et al, 2017), roach (Nikoleris et al, 2016), yellow perch (Lynn et al, 2008), rare minnow (Wang et al, 2010) and fathead minnow (Filby et al, 2007;Leet et al, 2015;Feswick et al, 2016). A downregulation of cyp19a1 correlates to depressed synthesis of endogenous estradiol (Villeneuve, 2016), which is a commonly observed endpoint in EE 2 exposure in fish (Gillio Meina et al, 2013;Wang et al, 2019).…”

“…A downregulation of cyp19a1 correlates to depressed synthesis of endogenous estradiol (Villeneuve, 2016), which is a commonly observed endpoint in EE 2 exposure in fish (Gillio Meina et al, 2013;Wang et al, 2019). This depression of E 2 synthesis may retard follicle growth in developing fish (Cosme et al, 2015). The response of cyp19a1 to EE 2 exposure is variable and impacted by exposure dose and duration, life stage of fish, and species (Johns et al, 2009;Trubiroha et al, 2012;Nikoleris et al, 2016), but the correlation between transcript levels of this gene and circulating plasma E 2 levels are well established in the literature (Perkins et al, 2015;Muth-Köhne et al, 2016).…”

Introduction to Special Issue: Disruption of thyroid, sex steroid, and adrenal hormone systems and their crosstalk in aquatic wildlife

“…This Special Issue includes four research studies, all of fishes, which consider EDC impacts on reproduction from the wet bench to the field. In their study of Zebrafish, Cosme et al (2015) work within the AOP framework to elucidate the effect of the EDC, ethinylestradiol, and the phospholipase A2 inhibitor, quinacrine on spawning and other apical endpoints of reproductive fitness in adult fish. An article by Kennedy and Smyth (2015) presents the kinetics of plasma levels of estradiol-17b and testosterone after injection of the polycyclic aromatic hydrocarbon, benzo[a]pyrene, a persistent organic pollutant (POP), in mature male Rainbow Trout (Oncorhynchus mykiss).…”