Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
Department of Biomedical Engineering, Duke University, Durham, NC 27708, United States.
Reprod Toxicol. 2024 Aug;127:108609. doi: 10.1016/j.reprotox.2024.108609. Epub 2024 May 16.
Toxicants and some drugs can negatively impact reproductive health. Many toxicants haven't been tested due to lack of available models. The impact of many drugs taken during pregnancy to address maternal health may adversely affect fetal development with life-long effects and clinical trials do not examine toxicity effects on the maternal-fetal interface, requiring indirect assessment of safety and efficacy. Due to current gaps in reproductive toxicological knowledge and limitations of animal models, multi-cellular engineered living systems may provide solutions for modeling reproductive physiology and pathology for chemical and xenobiotic toxicity studies. Multi-cellular engineered living systems, such as microphysiological systems (MPS) and organoids, model of functional units of tissues. In this review, we highlight the key functions and structures of human reproductive organs and well-known representative toxicants afflicting these systems. We then discuss current approaches and specific studies where scientists have used MPS or organoids to recreate in vivo markers and cellular responses of the female and male reproductive system, as well as pregnancy-associated placenta formation and embryo development. We provide specific examples of organoids and organ-on-chip that have been used for toxicological purposes with varied success. Finally, we address current issues related to usage of MPS, emerging techniques for improving upon these complications, and improvements needed to make MPS more capable in assessing reproductive toxicology. Overall, multi-cellular engineered living systems have considerable promise to serve as a suitable, alternative reproductive biological model compared to animal studies and 2D culture.
有毒物质和一些药物会对生殖健康产生负面影响。由于缺乏可用的模型，许多有毒物质尚未经过测试。许多在怀孕期间用于解决产妇健康问题的药物的影响可能会对胎儿发育产生不利影响，并产生终身影响，临床试验并未检查毒性对母体-胎儿界面的影响，需要间接评估安全性和有效性。由于生殖毒理学知识的现有差距和动物模型的局限性，多细胞工程化活体系统可能为化学和外来化合物毒性研究提供生殖生理学和病理学建模的解决方案。多细胞工程化活体系统，如微生理系统 (MPS) 和类器官，模拟组织的功能单位。在这篇综述中，我们强调了人类生殖器官的关键功能和结构，以及影响这些系统的著名代表性有毒物质。然后，我们讨论了目前科学家使用 MPS 或类器官来重现女性和男性生殖系统以及与妊娠相关的胎盘形成和胚胎发育的体内标志物和细胞反应的方法和具体研究。我们提供了用于毒理学目的的类器官和器官芯片的具体示例，取得了不同程度的成功。最后，我们讨论了与 MPS 使用相关的当前问题、改进这些并发症的新兴技术，以及提高 MPS 评估生殖毒理学能力所需的改进。总体而言，多细胞工程化活体系统具有很大的潜力，可以替代动物研究和 2D 培养，成为一种合适的替代生殖生物学模型。
