A computational model of the hypothalamic - pituitary - gonadal axis in female fathead minnows (Pimephales promelas) exposed to 17α-ethynylestradiol and 17β-trenbolone
1 Division of Environmental and Biomolecular Systems, Oregon Health & Science University, Beaverton, OR, 97006, USA
2 Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida, Gainesville, FL, 32611, USA
3 U.S. EPA, Mid-Continent Ecology Division, Duluth, MN, 55804, USA
4 Institute for the Environment, Brunel University, Uxbridge, Middlesex, UB8 3PH, UK
5 Department of Forestry and Natural Resources, Purdue University, Lafayette, IN, 47907, USA
6 Department of Animal & Avian Sciences, University of Maryland, College Park, MD 20742 USA
7 U.S. EPA, Molecular Indicator Research Branch, Cincinnati, OH, 45268, USA
8 The McConnell Group c/o U.S. EPA NERL EERD, USA
BMC Systems Biology 2011, 5:63 doi:10.1186/1752-0509-5-63Published: 5 May 2011
Endocrine 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).
Using 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.
The 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.