Base for International Science and Technology Cooperation: Carson Cancer Stem Cell Vaccines R&D Center, Shenzhen Key Lab of Synthetic Biology, Department of Physiology, School of Basic Medical Sciences, Shenzhen University, Shenzhen 518055, China; Dongguan Key Laboratory of Environmental Medicine, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
Department of Family Planning, Second Clinical Medical College of Jinan University; Shenzhen People's Hospital, Shenzhen 518060, China.
Ecotoxicol Environ Saf. 2021 Mar 15;211:111946. doi: 10.1016/j.ecoenv.2021.111946. Epub 2021 Jan 25.
Increased applications of quantum dots (QDs) in the biomedical field have aroused attention for their potential toxicological effects. Although numerous studies have been carried out on the toxicity of QDs, their effects on reproductive and development are still unclear. In this study, we systematically evaluated the male reproductive toxicity and developmental toxicity of CdSe/ZnS QDs in BALB/c mice. The male mice were injected intravenously with CdSe/ZnS QDs at the dosage of 2.5 mg/kg BW or 25 mg/kg BW, respectively, and the survival status, biodistribution of QDs in testes, serum sex hormone levels, histopathology, sperm motility and acrosome integrity was measured on Day 1, 7, 14, 28 and 42 after injection. On Day 35 after treatment, male mice were housed with non-exposed female mice, and then offspring number, body weight, organ index and histopathology of major organs, blood routine and biochemical tests of offspring were measured to evaluate the fertility and offspring health. The results showed that CdSe/ZnS QDs could rapidly distribute in the testis, and the fluorescence of QDs could still be detected on Day 42 post-injection. QDs had no adverse effect on the structure of testis and epididymis, but high-dose QDs could induce apoptosis of Leydig cells in testis at an early stage. No significant differences in survival of state, body weight organ index of testis and epididymis, sex hormones levels, sperm quality, sperm acrosome integrity and fertility of male mice were observed in QDs exposed groups. However, the development of offspring was obviously influenced, which was mainly manifested in the slow growth of offspring, changes in organ index of main organs, and the abnormality of liver and kidney function parameters. Our findings revealed that CdSe/ZnS QDs were able to cross the blood-testis barrier (BTB), produce no discernible toxic effects on the male reproductive system, but could affect the healthy growth of future generations to some extent. In view of the broad application prospect of QDs in biomedical fields, our findings might provide insight into the biological safety evaluation of the reproductive health of QDs.
量子点 (QDs) 在生物医学领域的应用日益广泛,其潜在的毒理学效应引起了人们的关注。尽管已经有大量关于 QDs 毒性的研究,但它们对生殖和发育的影响仍不清楚。在这项研究中,我们系统地评估了 CdSe/ZnS QDs 在 BALB/c 小鼠中的雄性生殖毒性和发育毒性。雄性小鼠分别静脉注射 2.5mg/kg BW 和 25mg/kg BW 的 CdSe/ZnS QDs,在注射后第 1、7、14、28 和 42 天测量 QDs 在睾丸中的生存状态、分布、血清性激素水平、组织病理学、精子活力和顶体完整性。在治疗后第 35 天,雄性小鼠与未暴露的雌性小鼠交配,然后测量后代数量、体重、主要器官的器官指数和组织病理学、后代的血常规和生化检查,以评估生育能力和后代健康。结果表明,CdSe/ZnS QDs 能够迅速分布在睾丸中,并且在注射后第 42 天仍能检测到 QDs 的荧光。QDs 对睾丸和附睾的结构没有不良影响,但高剂量 QDs 可在早期诱导睾丸间质细胞凋亡。在 QDs 暴露组中,雄性小鼠的生存状态、睾丸和附睾的体重器官指数、性激素水平、精子质量、精子顶体完整性和生育能力均无显著差异。然而,后代的发育明显受到影响,主要表现为后代生长缓慢、主要器官的器官指数改变以及肝肾功能参数异常。我们的研究结果表明,CdSe/ZnS QDs 能够穿过血睾屏障 (BTB),对雄性生殖系统没有明显的毒性作用,但在某种程度上会影响后代的健康生长。鉴于 QDs 在生物医学领域的广泛应用前景,我们的研究结果可能为 QDs 对生殖健康的生物学安全性评估提供一些启示。