淡化海水对雄性大鼠生殖系统影响的研究

DDesalinated seawater is an important water supply resource for solving the shortage of fresh water. In recent years, desalination industry has developed rapidly in China. Desalinated seawater originates from complex seawater with high concentrations of boron. The reverse osmosis method is currently used as a mainstream desalinated seawater treatment process and cannot completely remove boron. The content of boron in the desalinated seawater treated by reverse osmosis is about 3-5 times higher than the specified value of “Drinking Water Hygiene Standard” in china. Therefore, the high concentrations of boron are a common problem resulting from reverse osmosis desalination of seawater product water. However, there is currently lack of research on the health effects of high boron in desalinated seawater. This study assumes that desalinated seawater treated by reverse osmosis may have a negative effect on the male reproductive system due to high concentrations of boron. By establishing a model of long-term consumption of desalinated seawater in male rats, the impact of desalinated seawater on male reproduction are analyzed systematically from multiple levels of testicular tissue morphology, sperm quality, and enzyme markers, and so on. Meanwhile, the mechanisms of desalinated seawater toxicity are explored at the molecular level, by determing the key factors/protein expression in the hypothalamic-pituitary-testicular axis (HPG) and two pathways of LH-LHR-cAMP-PKA and LH-LHR-Ca2+-PKC, related to androgen synthesis in spermatogenesis. In addition, by comparing the similarities and differences between desalinated seawater samples and the simulated water samples with the same boron concentrations, the correlation between boron concentrations of desalinated seawater and male reproductive effects are explored. This study will fill the toxicological gaps in desalinated seawater for the effects of boron on male reproductive system. It will also provide a scientific and experimental basis for the study of health risks and safety evaluation of seawater desalination.

淡化海水作为解决淡水紧缺的一个重要供水资源，近年来在我国迅速发展。原水（海水）中矿物质复杂，硼含量较高。反渗透法作为主要淡化处理工艺除硼效果不佳，其产品水中硼含量超出我国现行《生活饮用水卫生标准》中规定值约3-5倍。高硼含量是反渗透法处理淡化海水普遍面临的问题，但目前缺乏相应的健康影响研究。本研究以此为切入点，通过建立雄性大鼠长期饮用淡化海水染毒模型，从睾丸组织形态、精子质量、标志性酶、生育力等多方面解析淡化海水对雄性生殖功能的影响；并从调控精子发生的下丘脑-垂体-睾丸轴（HPG）、雄激素合成的两个调节通路LH-LHR-cAMP-PKA和LH-LHR-Ca2+-PKC方面进行毒性机制初步研究。同时，通过比较淡化海水与相同硼含量的模拟水样毒性效应，阐明淡化海水硼含量和雄性生殖影响的相关性。本研究填补了淡化海水对雄性生殖系统影响的研究空白，为其健康风险研究及安全性评价提供了实验基础及科学依据。

淡化海水作为解决淡水紧缺的一个重要供水资源，近年来迅速发展。原水（海水） 中矿物质复杂，硼含量较高。反渗透法作为主要淡化处理工艺除硼效果不佳。本研究通过建立雄性大鼠长期饮用淡化海水暴露模型，从组织形态、精子质量、标志性酶、生育力等多方面解析淡化海水对雄性生殖功能的影响；并从影响雄性生殖的主要调控机制HPG轴及两个重要调节通路LH-LHR-cAMP-PKA和LH-LHR-Ca2+-PKC中关键因子及转录组进行毒性机制初步研究；通过比较淡化海水与相同硼含量的模拟水样毒性效应，阐明淡化海水硼含量和雄性生殖影响的相关性；同时开展了28天短期高剂量硼暴露实验，与长期饮用淡化海水的动物实验进行对比研究。结果表明，受试淡化海水样品中平均硼含量为1.74mg/L，高于《生活饮用水卫生标准》(GB5749-2006)限值；在本研究暴露条件下，长期饮用淡化海水对于雄性生殖器官组织形态、精子形态、生育力均无影响，睾丸标志酶SDH、G-6-PD、LDH-X活性降低并影响到精子能量供应，继而影响到精子成熟程度及运动能力，该结果可能与高硼含量有关；本研究暴露条件对于HPG轴上性激素无明显影响，但可能引起LHR高表达，激活PKA、PKC通路。但PKA、PKC及下游p-CREB的表达水平可能受通路中多位点关键因子的影响; 转录组结果也发现饮用淡化海水组大鼠差异基因4785个（上调2449个，下调2336个），高于其他暴露组; 差异基因功能富集分析发现饮用淡化海水组大鼠与对照组相比显著性较高差异基因涉及到雄性生殖细胞的产生、精子发生、精子细胞发育、精子细胞分化等生物过程。90天低剂量长期暴露结果与后续28天高剂量短期硼暴露结果对比发现: 短时间暴露后硼主要分布于血液，存在剂量依赖性；长时间暴露后血液与靶器官组织中均有分布；硼暴露剂量与暴露时间对于SDH均有明显影响，SDH在硼产生的雄性生殖健康影响中可作为重要的判定指标; G3PDH、MDH变化状况可能会受硼暴露剂量影响，硼暴露时间对其影响不明显。本研究填补了淡化海水对雄性生殖系统影响的研究空白，为其健康风险研究及安全性 评价提供了实验基础及科学依据。