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AOP Development; Aromatase Inhibition and Androgen Receptor Agonism Lead to Male Biased Sex Ratio Via Impacts on Gonad Differentiation
Citation:
Santana Rodriguez, K., G. Ankley, D. Miller, AND Dan Villeneuve. AOP Development; Aromatase Inhibition and Androgen Receptor Agonism Lead to Male Biased Sex Ratio Via Impacts on Gonad Differentiation. SETAC North America 42nd Annual meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.17105597
Impact/Purpose:
Poster presented to the SETAC North America 42nd Annual meeting November 2021. Endocrine active chemicals are of special concern for chemical hazard evaluation. A number of in vitro approaches have been developed to rapidly screen chemicals for biological activities that can lead to endocrine disruption, such as ability to inhibit steroid biosynthesis or ability to bind to steroid hormone receptors. A number of adverse outcome pathways (AOPs) have linked such activities to reproductive hazards in adult fish. The present study expands on these efforts to develop AOPs that link exposure to specific types of endocrine disruptors (androgen receptor agonsits and aromatase inhibitors), during the period of sexual differentiation, to male biased sex ratios. Additionally, population modeling was used to project the potential hazards to population sustainability. The products of this research support the needs of OCSPP to identify and understand the hazards endocrine disrupting chemicals pose to aquatic ecosystems.
Description:
In teleost fish, the balance between steroidal estrogens and androgens is essential during sexual differentiation and this balance is in turn dependent on the availability and activity of steroid synthesizing enzymes such as aromatase, the enzyme responsible for the conversion of androgens to estrogens. Given the important role that steroid hormone signaling plays in sexual differentiation, it is not surprising that exposure to some types of endocrine active substances during critical periods of development can result in skewed phenotypic sex ratios. The present study utilized the adverse outcome pathway (AOP) framework to organize available evidence linking aromatase inhibition and androgen receptor agonism to male-biased sex ratios in fish. A literature search was conducted using ‘aromatase inhibition’, ‘male biased sex ratios’ and ‘androgen sex reversal’ in combination with ‘fish’ as the main keywords. Publications describing exposures or experimental treatments of teleost fish during the critical period of sexual differentiation and including both gonadal histology and an indicator of final population sex ratio were included as relevant. Additionally, a novel mathematical model linking male biased sex ratio to projected alterations in population trajectories was developed. Collectively, there was moderate to high scientific support for the causal linkages between aromatase inhibition or androgen receptor agonism and male biased sex ratios in fish. These two AOPs, focused on impacts during the period of sexual differentiation (i.e., early life stages), complement a broader network of AOPs documenting potential hazards that endocrine active chemicals pose to fish, thereby further supporting predictive approaches to hazard and risk assessment. The contents of this abstract neither constitute, nor necessarily reflect, official US EPA policy.
URLs/Downloads:
DOI: AOP Development; Aromatase Inhibition and Androgen Receptor Agonism Lead to Male Biased Sex Ratio Via Impacts on Gonad Differentiation
2021 SETAC POSTER DRAFT- KELVIN J. SANTANA RODRIGUEZ.PDF (PDF, NA pp, 1226.156 KB, about PDF)