摘要：大量研究已证明人们长期生活在含有纳米TiO2的环境下，纳米TiO2会通过呼吸、消化、皮肤等途径入侵体内，并通过血液循环在卵巢中沉积，造成生殖毒性，但这种生殖毒性机制尚不明确。本文用不同浓度的纳米TiO2 (1。25、2。5、5 mg/kg BW）连续60天灌胃处理雌性小鼠后用显微镜观察小鼠卵巢组织切片对各级卵泡及黄体计数，并通过分析卵巢卵泡发育和细胞凋亡相关因子的蛋白表达水平变化，以研究纳米TiO2长期暴露是否引起卵巢卵泡发育障碍并探讨其分子作用机制。实验观察到纳米TiO2暴露后卵巢萎缩，初级卵泡和次级卵泡发育障碍，卵巢细胞的不规则排列和卵泡腔的形状不规则，出现大量卵泡闭锁等病理学改变。进一步研究显示在与细胞增殖、分化相关的TGF-β/PI3K/AKT/mTOR信号通路中，与促卵泡卵母细胞生长发育因子PI3K、AKT、p-mTOR、mTOR、p-p70S6K1、p70S6K、PTEN、p-rpS6、rpS6表达下调，促细胞凋亡因子TGF-β1、TGF-βR1、Fox03a表达上调。这些结果表明纳米TiO2颗粒长期暴露会导致卵泡卵细胞凋亡和卵巢功能损伤，为深入了解纳米TiO2导致卵巢卵泡发育障碍的分子机制提供理论依据。92923

关键词：纳米TiO2；卵巢组织；卵泡发育；细胞凋亡；蛋白表达

Abstract: Numerous studies have confirmed that long-term living in the environment exposure to titanium dioxide nanoparticles (TiO2 NPs), the NPs can penetrate through respiratory and digestive system and the skin into the body, and possibly through blood circulation are accumulated in the ovaries, which led to reproductive toxicity。 However, the mechanism of reproductive toxicity is still unclear。 In this study, mice were exposed to TiO2 NPs with different doses (1。25, 2。5, or 5 mg/kg BW) by intragastric administration for 60 consecutive days。 After that, the mouse ovarian tissue slices were observed by microscope and ovarian follicle, corpus luteum uterus index and ovarian index of the mice were counted。 By analyzing the changes of the protein expression levels of follicular development and apoptosis related factors, to study whether the long-term exposure to TiO2 NPs lead to disorder of follicular development and explore its molecular mechanism。 The observations suggested that exposure to TiO2 NPs could result in ovarian atrophy, disturbance of primary and second follicle development, irregular arrangement of cells and a shapeless follicular antrum。 It also led to a large number of follicular atresia and other pathological changes。 Further studies have shown that in TGF-β / PI3K / AKT / mTOR signaling pathways associated with cell proliferation and differentiation, the expression of PI3K, AKT, p-mTOR, mTOR, p-p70S6K1, p70S6K, TGF-β1, TGF-βR1, p-rpS6 and rpS6 related with follicular growth and development were upregulated, and the expressions of PTEN、Fox03a related with apoptosis were downregulated。 These results suggested that long-term exposure to titanium dioxide nanoparticles led to the the apoptosis of oocytes and the damage of ovarian function, which provides a theoretical basis for understanding the molecular mechanism of TiO2 induced follicular development disorder。

Key words: Titanium dioxide nanoparticles; Mice; Ovarian; Follicular development; Cell apoptosis; 

目录

第一部分:纳米TiO2的毒理学研究进展 4

1 纳米TiO2的特性及应用 4

2 纳米TiO2颗粒进入机体的方式 4

2。1 皮肤吸收 4

2。2 呼吸系统吸入 4

2。3 消化系统吸入 5

3 纳米TiO2的毒性作用