A 3-D tissue model of breast morphogenesis for replacing animals in testing for endocrine disrupting substances

荷尔蒙是一种天然化学物质，它将信息从大脑或各种(内分泌)腺体传递到体内的细胞。内分泌干扰物质(EDS)干扰荷尔蒙传递信息。婴儿在母亲体内的发育情况？子宫非常依赖于正确的极低水平的激素。任何出现的EDS都可能破坏发送给婴儿细胞的正确发育信号，并导致问题。内分泌学会在2009年发表了一份关于内分泌干扰物质(EDS)的声明，援引了预防原则。目前测试EDS对子宫发育影响的唯一可靠方法是使用动物。由于很难对活体胚胎进行直接测量，研究不得不牺牲处于不同发育阶段的动物。我们希望开发一种乳腺组织模型，使用商业上可获得的细胞系中的人类细胞，这样我们就可以测试EDS，看看它们是否会影响发育。这是建立在我们之前基于2D细胞培养的研究结果基础上的，该研究检测一种化学物质是否是一种模仿女性和/或男性性激素的EDS。这已经取代了许多动物实验。然而，为了检测EDS在发育过程中可能造成的损害，我们需要建立一种新型的细胞培养模型，使我们能够设计、控制和观察模型组织，该模型组织由生活中在真实组织中发现的不同类型的细胞组成，并表现出相同的有趣的复杂导管分支结构。这项任务将需要具有组织培养、显微镜使用和测量科学技能的科学家的合作努力。我们位于阿尔斯特的大学刚刚投资654K购买了一台新的显微镜和组织工程设备，这将帮助我们实现这一任务。开发和提供该设备的国际知名公司徕卡表示有兴趣支持和帮助我们完成这项任务。因此，我们要求NC3R提供资金，以寻找熟练的人力和消耗品。我们预计最终结果将导致一个测试系统，使我们能够可靠地识别有害剂量的EDSS，而不需要使用动物，同时允许我们直接观察EDS造成的破坏过程。这可能会为EDSS在现实生活中如何运作提供进一步的线索。

Hormones are natural chemicals which carry messages to cells in the body from the brain or various (endocrine) glands. Endocrine disrupting substances (EDS) interfere with the passing of messages by hormones. Development of babies in their mothers? wombs is very dependent on the correct very low level of hormone. Any EDS present may corrupt the correct developmental signal being sent to the cells of the baby and cause problems. The Endocrine Society in 2009 published a statement on endocrine disrupting substances (EDS) invoking the Precautionary Principle.The only reliable way at present to test for the effects of EDS on development in the womb is to use animals. Because it is very difficult to perform direct measurements on living embryos, studies have to sacrifice animals at different stages of development. We wish to develop a model of breast tissue, using human cells from commercially available cell lines, so that we can test EDS and see if they affect development. This is building on results from our previous research based on 2D cell cultures detecting whether a chemical is an EDS that mimics the female and/or male sex hormones. This has already replaced many animal experiments. However, to detect the damage that can be caused by EDS during development we need to establish a new type of cell culture model that allows us to engineer, control and observe a model tissue consisting of the different types of cells found in the real tissue during life and exhibiting the same intriguing complex ductal branching structure. This task will require a cooperative effort by scientists with skills in tissue culture, microscope usage and measurement science. Our University in Ulster has just invested #654k in a new microscope and tissue engineering facility that will help us to achieve this task. The internationally renowned company, Leica, who developed and provides this equipment, expressed their interest in supporting and helping us in this task. We are therefore asking the NC3Rs for funds to find skilled manpower and consumable items.We anticipate that the end result will lead to a testing system that enables us to reliably identify harmful doses of EDSs without the need to use animals and at the same time allow us to directly observe the damaging process caused by EDS. This will potentially give further clues on how EDSs work in real life.