Gender-dependent reproductive toxicity of copper metal-organic frameworks and attenuation by surface modification.
Gender-dependent reproductive toxicity of copper metal-organic frameworks and attenuation by surface modification.
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DOI：
10.1039/d1nr01008e
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发表时间：
2021-04
期刊：
影响因子：
6.7
通讯作者：
Xiaotian Ji;Yousheng Mo;Haishan Li;Wanling Zhao;Aiqi Zhong;Shengqing Li;Qi Wang;Xiaopin Duan;Jisheng Xiao
中科院分区：
文献类型：
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作者：
Xiaotian Ji;Yousheng Mo;Haishan Li;Wanling Zhao;Aiqi Zhong;Shengqing Li;Qi Wang;Xiaopin Duan;Jisheng Xiao
金属有机骨架材料在药物传递、疾病诊断和治疗等方面有着广泛的应用前景。然而，它们对生殖系统的影响尚不清楚，这阻碍了它们进一步的临床应用。本研究表明，反复皮下注射铜MOFs （HKUST-1）对雄性生殖系统的毒性高于雌性生殖系统，导致雌性小鼠精管组织学破坏，精子生成障碍，不可逆的精子形态异常和妊娠率降低，但雌性小鼠只有轻微的卵泡功能障碍和妊娠并发症。有趣的是，叶酸修饰HKUST-1可以减轻生殖毒性，甚至改善妊娠和胎儿发育。本研究证实了HKUST-1对生殖系统的性别依赖性毒性，叶酸修饰可减轻其生殖毒性，为我们深入了解铜MOFs的生殖毒性提供了依据，也为提高铜MOFs的生物相容性提供了指导和可行的方法，具有潜在的医学应用价值。
Metal-organic frameworks (MOFs) as promising materials have been widely used in drug delivery, disease diagnosis and therapy; however, their effects on the reproductive system remain unknown, which hinders their further clinical applications. Here we show that repeated subcutaneous injections of copper MOFs (HKUST-1) induce higher toxicity into the male reproductive system relative to the female reproductive system, with disrupted seminiferous tubule histology, sperm generation disorder, irreversible sperm morphological abnormities and reduced pregnancy rate but only slight follicle dysfunction and pregnancy complications in female mice. Interestingly, the modification of HKUST-1 with folic acid attenuates the reproductive toxicity and even improves pregnancy and fetus development. This study confirms the gender-dependent toxicity of HKUST-1 to the reproductive system, and that folic acid modification could relieve the reproductive toxicity, thus providing us a deep understanding of reproductive toxicity of copper MOFs, and also a guideline and feasible way to improve the biocompatibility of copper MOFs for potential medical use.