Hatai Dylan, Levenson Max T, Rehan Virender K, Allard Patrick
UCLA Molecular Toxicology Interdepartmental Program, University of California Los Angeles, Los Angeles, CA, USA.
Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA.
Curr Opin Toxicol. 2024 Jun;38. doi: 10.1016/j.cotox.2024.100465. Epub 2024 Feb 8.
Reproduction is a remarkably intricate process involving the interaction of multiple cell types and organ systems unfolding over long periods of time and that culminates with the production of gametes. The initiation of germ cell development takes place during embryogenesis but only completes decades later in humans. The complexity inherent to reproduction and its study has long hampered our ability to decipher how environmental agents disrupt this process. Single-cell approaches provide an opportunity for a deeper understanding of the action of toxicants on germline function and analyze how the response to their exposure is differentially distributed across tissues and cell types. In addition to single-cell RNA sequencing, other single-cell or nucleus level approaches such as ATAC-sequencing and multi-omics have expanded the strategies that can be implemented in reproductive toxicological studies to include epigenomic and the nuclear transcriptomic data. Here we will discuss the current state of single-cell technologies and how they can best be utilized to advance reproductive toxicological studies. We will then discuss case studies in two model organisms ( and mouse) studying different environmental exposures (alcohol and e-cigarettes respectively) to highlight the value of single-cell and single-nucleus approaches for reproductive biology and reproductive toxicology.
生殖是一个极其复杂的过程，涉及多种细胞类型和器官系统的相互作用，这个过程会持续很长时间，并最终产生配子。生殖细胞发育的起始发生在胚胎形成过程中，但在人类中要几十年后才会完成。生殖过程本身固有的复杂性及其研究长期以来一直阻碍着我们解读环境因素如何干扰这一过程的能力。单细胞方法为更深入地了解毒物对生殖系功能的作用提供了机会，并分析对毒物暴露的反应如何在不同组织和细胞类型中差异分布。除了单细胞RNA测序外，其他单细胞或细胞核水平的方法，如ATAC测序和多组学技术，已经扩展了可用于生殖毒理学研究的策略，将表观基因组和核转录组数据也纳入其中。在此，我们将讨论单细胞技术的现状以及如何最好地利用这些技术来推进生殖毒理学研究。然后，我们将讨论在两种模式生物（果蝇和小鼠）中分别研究不同环境暴露（酒精和电子烟）的案例，以突出单细胞和单细胞核方法在生殖生物学和生殖毒理学中的价值。
