John Wiley & Sons, Ltd.

Tissue explant co‐culture model of the hypothalamic‐pituitary‐gonadal‐liver axis of the fathead minnow (Pimephales promelas) as a predictive tool for endocrine disruption

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Endocrine disrupting compounds (EDCs) can impact the reproductive system by interfering with the hypothalamic‐pituitary‐gonadal (HPG) axis. While in vitro testing methods have been developed to screen chemicals for endocrine disruption, extrapolation of in vitro response to in vivo action shows inconsistent accuracy. We describe here our tissue co‐culture of the fathead minnow (Pimephales promelas) HPG axis and liver (HPG‐L) as a tissue explant model that mimics in vivo results. Brain (hypothalamus), pituitary, gonad, and liver tissue explants from adult fish were examined for function both individually and in co‐culture to determine combinations and conditions that could replicate in vivo behavior. Only co‐cultures had the ability to respond to an EDC, trenbolone, similarly to in vivo studies, based upon estradiol, testosterone, and vitellogenin production trends, where lower exposure doses suppressed hormone production but higher doses increased production resulting in distinctive U‐shaped curves. These data suggest that a co‐culture system with all components of the HPG‐L axis can be used as a link between in vitro and in vivo studies to predict endocrine system disruption in whole organisms. This tissue based HPG‐L system acts as a flexible deconstructed version of the in vivo system for better control and examination of the minute changes in system operation and response upon EDC exposure with options to isolate, interrogate, and recombine desired components. This article is protected by copyright. All rights reserved

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