Zinc eluted from glassware is a risk factor for embryo development in human and animal assisted reproduction

In assisted reproduction, many factors in the culture environment, including light, temperature, pH, and culture media, can reduce preimplantation embryo viability. Laboratory glassware is also a known risk factor for in vitro embryos; however, the underlying mechanisms that disrupt embryonic development remain unclear. We identified Zn eluted from glassware as an embryotoxic substance. In mouse embryos, Zn-induced delayed development, abnormalities in chromosome segregation, cytokinesis, zygotic gene activation (e.g., Zscan4c and murine endogenous retrovirus with leucine, also known as MERVL), and aberrantly upregulated developmental gene expression (e.g., Hoxa1, Hoxb9, T, and Fgf8) that could be mediated through metal regulatory transcription factors (e.g., Mtf1). Subsequently, Zn exposure led to significantly reduced blastocyst formation. Postimplantation, Zn-exposed embryos were associated with normal birth rates, however, the birth weight increased by an average of 18% compared with embryos cultured without Zn. Furthermore, Zn exposure affected the development of bovine and human embryos, with species-based variation in the strength and timing of these effects. To mitigate these embryotoxic effects, we identified a method to prevent glass toxicity using chelating agents. This research not only highlights the importance of risk control in embryo culture but also facilitates the development of safe and effective methods for assisted reproduction. Overall design: Gene expression analysis of preimplantation embryos exposed with zinc metal ion in vitro.

在辅助生殖领域，培养环境中的诸多因素——包括光照、温度、pH值及培养液——均会降低植入前胚胎的存活能力。实验室玻璃器皿亦是体外胚胎培养的已知风险因素，但其干扰胚胎发育的具体分子机制仍未明确。本研究确认从玻璃器皿中溶出的锌（Zinc）为一类胚胎毒性物质。在小鼠胚胎中，锌暴露会诱导发育延迟，引发染色体分离、胞质分裂异常，以及合子基因激活（如Zscan4c与含亮氨酸的小鼠内源性逆转录病毒，亦称MERVL）异常，并异常上调发育相关基因的表达（如Hoxa1、Hoxb9、T及Fgf8），上述效应可通过金属调控转录因子（如Mtf1）介导。后续实验显示，锌暴露会显著降低囊胚形成率。植入后阶段，经锌暴露的胚胎出生率与对照组无显著差异，但新生幼崽的平均体重较未暴露锌的胚胎组升高18%。此外，锌暴露会影响牛及人类胚胎的发育，且该效应的强度与出现时机存在物种特异性差异。为缓解此类胚胎毒性效应，本研究开发出一种利用螯合剂规避玻璃器皿毒性的方法。本研究不仅凸显了胚胎培养过程中风险管控的重要性，同时也为辅助生殖领域安全高效培养体系的研发提供了助力。实验整体设计：体外暴露于锌离子的植入前胚胎基因表达分析。