Abstract
BackgroundEndocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17α-ethynylestradiol is a synthetic estrogen used in birth control pills. 17β-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. Both 17α-ethynylestradiol and 17β-trenbolone have been found in the aquatic environment and affect fish reproduction. In this study, we developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas), a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17α-ethynylestradiol) or androgens (i.e., 17β-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17β-estradiol and testosterone) and vitellogenin (a precursor to egg yolk proteins).ResultsUsing Markov Chain Monte Carlo simulations, the model was calibrated with data from unexposed, 17α-ethynylestradiol-exposed, and 17β-trenbolone-exposed FHMs. Four Markov chains were simulated, and the chains for each calibrated model parameter (26 in total) converged within 20,000 iterations. With the converged parameter values, we evaluated the model's predictive ability by simulating a variety of independent experimental data. The model predictions agreed with the experimental data well.ConclusionsThe physiologically-based computational model represents the hypothalamic-pituitary-gonadal axis in adult female FHM robustly. The model is useful to estimate how estrogens (e.g., 17α-ethynylestradiol) or androgens (e.g., 17β-trenbolone) affect plasma concentrations of 17β-estradiol, testosterone and vitellogenin, which are important determinants of fecundity in fish.
Highlights
Endocrine disrupting chemicals are known to affect reproduction in fish. 17a-ethynylestradiol is a synthetic estrogen used in birth control pills. 17b-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock
To better understand the dynamics of the HPG axis in female FHMs and to facilitate the evaluation of adverse outcomes on reproduction from both estrogenic and androgenic endocrine disrupting chemicals (EDCs) exposure, we developed a physiologically based computational model to simulate key reproductive endpoints, such as plasma concentrations of E2, T, and VTG, in adult female FHMs
We found that gnrh promoters contain several androgen response element (ARE) half sites [24]
Summary
Endocrine disrupting chemicals (e.g., estrogens, androgens and their mimics) are known to affect reproduction in fish. 17a-ethynylestradiol is a synthetic estrogen used in birth control pills. 17b-trenbolone is a relatively stable metabolite of trenbolone acetate, a synthetic androgen used as a growth promoter in livestock. We developed a physiologically-based computational model for female fathead minnows (FHM, Pimephales promelas), a small fish species used in ecotoxicology, to simulate how estrogens (i.e., 17a-ethynylestradiol) or androgens (i.e., 17b-trenbolone) affect reproductive endpoints such as plasma concentrations of steroid hormones (e.g., 17b-estradiol and testosterone) and vitellogenin (a precursor to egg yolk proteins). In vertebrates, such as fish, the hypothalamic-pituitarygonadal (HPG) axis controls reproductive processes through a variety of hormones which act on target tissues directly or indirectly [1,2]. A seven-year, whole-lake experiment conducted in Canada [17] showed that chronic exposure of FHMs to 5 - 6 ng EE2/L led to near-extinction of this species from the lake
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