Physiologically based computational modeling of the hypothalamic-pituitary-gonadal axis in fathead minnows

Endocrine‑disrupting chemicals (EDCs) interfere with reproduction in fish by altering signals in the hypothalamic‑pituitary‑gonadal (HPG) axis. This dissertation examines the effects of estrogenic EDCs, including natural 17β‑estradiol (E2) and synthetic 17α‑ethynylestradiol (EE2), as well as the androgenic compound 17β‑trenbolone (TB), on male and female fathead minnows. Physiologically based computational models of the HPG axis were developed for unexposed and exposed fish and calibrated using experimental data. Model predictions aligned well with observed reproductive endpoints, demonstrating robust performance. A third model linking vitellogenin uptake to oocyte growth further connected biochemical disruption to reproductive outcomes. Together, these models provide tools for predicting reproductive effects of EDCs and support regulatory evaluation and monitoring efforts.