建立组织外植体的共培养模型(in vitro)用于预测内分泌干扰效应(in vivo)：以黑头软口鲦(Pimephales promelas)的下丘脑-垂体-性腺（HPG）轴内分泌干扰作用为例

内分泌干扰物 （Endocrine Disrupting Compounds, EDCs）可以通过干扰下丘脑-垂体-性腺（HPG）轴来影响生殖系统。虽然目前已有筛选内分泌干扰物的体外检测方法，但这些方法在用于体内实验时却有着不稳定的准确性。本文记录了以黑头呆鱼（Pimephales promelas）的下丘脑-垂体-性腺轴与肝（HPG-L）的共培养组织作为组织外植体来模拟体内反应的结果。我们对成年鱼的大脑（下丘脑），垂体，性腺和肝进行了单独和共同培养的检测来确定可以在体内重复的情况与组合。只有共培养体表现出去甲雄三烯醇酮对于雌二醇，睾酮和卵黄生成素生成趋势的影响。较低的暴露剂量会抑制激素生成，而较高的暴露剂量则会促进激素生成，形成U型作用曲线。这些数据表明下丘脑-垂体-性腺-肝轴的全部组织的共同培养可以作为体内实验与体外实验的连接，从而预测在完整生物体内内分泌系统的扰乱。本实验中以组织为基础的下丘脑-垂体-性腺-肝系统作为一个灵活的体内系统的解构版本得到了更好的实验控制。通过分离、审查和重组需要的组织，我们能够检测到生物系统功能与对于内分泌干扰物反应中的微小变化。
精选自Theresa K. Johnston, Edward Perkins, Duncan C. Ferguson, Donald M. Cropek. 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. Environmental Toxicology and Chemistry: Volume 35, Issue 10, pages 2530–2541, October 2016. DOI: 10.1002/etc.3415
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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

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.
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