A computational model of the hypothalamic-pituitary-gonadal axis in male fathead minnows exposed to 17alpha-ethinylestradiol and 17beta-estradiol.
Estrogenic chemicals in the aquatic environment have been shown to cause a variety of reproductive anomalies in fish including full sex reversal, intersex, and altered population sex ratios. Two estrogens found in the aquatic environment, 17alpha-ethinylestradiol (EE(2)) and 17beta-estradiol (E(2)), have been measured in wastewater treatment effluents and have been shown to cause adverse effects in fish. To further our understanding of how estrogen exposure affects reproductive endpoints in the male fathead minnow (FHM, Pimephales promelas), a physiologically based computational model was developed of the hypothalamic-pituitary-gonadal (HPG) axis. Apical reproductive endpoints in the model include plasma steroid hormone and vitellogenin concentrations. Using Markov chain Monte Carlo simulation, the model was calibrated with data from unexposed FHM, and FHM exposed to EE(2) and E(2). Independent experimental data sets were used to evaluate model predictions. We found good agreement between our model predictions and a variety of measured reproductive endpoints, although the model underpredicts unexposed FHM reproductive endpoint variances, and overpredicts variances in estrogen-exposed FHM. We conclude that this model provides a robust representation of the HPG axis in male FHM.
Division of Environmental and Biomolecular Systems, Department of Science and Engineering, Oregon Health & Science University, West Campus, Beaverton, Oregon 97006, USA. watanabe@ebs.ogi.edu
Karen H
KH
Watanabe
Zhenhong
Z
Li
Kevin J
KJ
Kroll
Daniel L
DL
Villeneuve
Natàlia
N
Garcia-Reyero
Edward F
EF
Orlando
Maria S
MS
Sepúlveda
Timothy W
TW
Collette
Drew R
DR
Ekman
Gerald T
GT
Ankley
Nancy D
ND
Denslow
D000818:Animals; D002138:Calibration; D003198:Computer Simulation; D003530:Cyprinidae / Q000378:metabolism*; D004958:Estradiol / Q000633:toxicity*; D004997:Ethinyl Estradiol / Q000633:toxicity*; D012739:Gonadal Steroid Hormones / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008390:Markov Chains; D008954:Models, Biological; D009010:Monte Carlo Method; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D025341:Principal Component Analysis; D015398:Signal Transduction / Q000187:drug effects; D014819:Vitellogenins / Q000097:blood; D014874:Water Pollutants, Chemical / Q000633:toxicity*
D012739:Gonadal Steroid Hormones; D014819:Vitellogenins; D014874:Water Pollutants, Chemical; D004997:Ethinyl Estradiol; D004958:Estradiol