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神经源性和神经保护药物的生殖毒性不良副作用:当前将人体类器官模型用作临床前模型潜在替代方法的应用情况。

The reprotoxic adverse side effects of neurogenic and neuroprotective drugs: current use of human organoid modeling as a potential alternative to preclinical models.

作者信息

Abady Mariam M, Jeong Ji-Seon, Kwon Ha-Jeong, Assiri Abdullah M, Cho Jongki, Saadeldin Islam M

机构信息

Organic Metrology Group, Division of Chemical and Material Metrology, Korea Research Institute of Standards and Science, Daejeon, Republic of Korea.

Department of Bio-Analytical Science, University of Science and Technology, Daejeon, Republic of Korea.

出版信息

Front Pharmacol. 2024 Jun 14;15:1412188. doi: 10.3389/fphar.2024.1412188. eCollection 2024.

DOI:10.3389/fphar.2024.1412188
PMID:38948466
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11211546/
Abstract

The management of neurological disorders heavily relies on neurotherapeutic drugs, but notable concerns exist regarding their possible negative effects on reproductive health. Traditional preclinical models often fail to accurately predict reprotoxicity, highlighting the need for more physiologically relevant systems. Organoid models represent a promising approach for concurrently studying neurotoxicity and reprotoxicity, providing insights into the complex interplay between neurotherapeutic drugs and reproductive systems. Herein, we have examined the molecular mechanisms underlying neurotherapeutic drug-induced reprotoxicity and discussed experimental findings from case studies. Additionally, we explore the utility of organoid models in elucidating the reproductive complications of neurodrug exposure. Have discussed the principles of organoid models, highlighting their ability to recapitulate neurodevelopmental processes and simulate drug-induced toxicity in a controlled environment. Challenges and future perspectives in the field have been addressed with a focus on advancing organoid technologies to improve reprotoxicity assessment and enhance drug safety screening. This review underscores the importance of organoid models in unraveling the complex relationship between neurotherapeutic drugs and reproductive health.

摘要

神经系统疾病的治疗严重依赖于神经治疗药物,但人们对其可能对生殖健康产生的负面影响存在显著担忧。传统的临床前模型往往无法准确预测生殖毒性,这凸显了对更具生理相关性系统的需求。类器官模型是同时研究神经毒性和生殖毒性的一种有前景的方法,它能深入了解神经治疗药物与生殖系统之间复杂的相互作用。在此,我们研究了神经治疗药物诱导生殖毒性的分子机制,并讨论了案例研究的实验结果。此外,我们探讨了类器官模型在阐明神经药物暴露所致生殖并发症方面的效用。讨论了类器官模型的原理,强调了它们在可控环境中重现神经发育过程和模拟药物诱导毒性的能力。该领域的挑战和未来展望也已得到阐述,重点是推进类器官技术以改善生殖毒性评估并加强药物安全性筛查。这篇综述强调了类器官模型在揭示神经治疗药物与生殖健康之间复杂关系方面的重要性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/19f41aa3c5f8/fphar-15-1412188-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/e6053d974090/fphar-15-1412188-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/819e1f71dee5/fphar-15-1412188-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/19f41aa3c5f8/fphar-15-1412188-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/e6053d974090/fphar-15-1412188-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/819e1f71dee5/fphar-15-1412188-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8d82/11211546/19f41aa3c5f8/fphar-15-1412188-g003.jpg

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