Departamento de Toxicología, Centro de Investigación y de Estudios avanzados del Instituto Politécnico Nacional (Cinvestav). Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Ciudad de México 07360, México.
Unidad de Microscopía Electrónica (LaNSE), Cinvestav. Av. Instituto Politécnico Nacional 2508, Col. San Pedro Zacatenco, Ciudad de México 07360, México.
Reprod Toxicol. 2020 Sep;96:399-412. doi: 10.1016/j.reprotox.2020.08.003. Epub 2020 Aug 13.
Titanium dioxide (TiO) and zinc oxide (ZnO) nanoparticles (NP) have been demonstrated to reach the ovary. However, the potential detrimental effects of these metal-based NP on ovarian antral follicles and whether they can be directly taken up by follicular cells are unknown. The aim of this study was to evaluate whether TiO and ZnO NP internalize into the antral follicle, and further compared any potential detrimental effects of either NP on growth, ultrastructure and viability of antral follicles. It has been described that TiO and ZnO NP induce oxidative stress, thus this study indirectly assessed whether oxidative stress was involved. Antral follicles were cultured with TiO (5, 25 and 50 μg/mL) or ZnO (5, 15 and 25 μg/mL) NP for 96 h. TiO NP were internalized and agglomerated into cells, increased follicle diameter and disrupted the cytoskeleton arrangement, effects that were partially prevented by a co-exposure with trolox. Moreover, ZnO NP partially dissolved into culture media, decreased follicle diameter, and disrupted cytoskeletal arrangement, and these effects were not prevented by trolox. Ultrastructural alterations induced by exposure to both NP were evidenced by impaired transzonal projections and swelling mitochondria. Oxidative stress mediates TiO NP-induced effects but not those from ZnO NP in antral follicle development. Our results suggest that both NP induced ovarian follicle toxicity through different toxic mechanisms, possibly due to a stimulation of ZnO NP solubility and agglomeration of TiO NP into the follicular cells.
二氧化钛（TiO）和氧化锌（ZnO）纳米颗粒（NP）已被证明可到达卵巢。然而，这些基于金属的 NP 对卵巢腔前卵泡的潜在有害影响，以及它们是否可以被卵泡细胞直接摄取，目前尚不清楚。本研究旨在评估 TiO 和 ZnO NP 是否能进入腔前卵泡，并进一步比较这两种 NP 对腔前卵泡生长、超微结构和活力的任何潜在有害影响。已经描述了 TiO 和 ZnO NP 会诱导氧化应激，因此本研究间接评估了氧化应激是否参与其中。将腔前卵泡与 TiO（5、25 和 50 μg/mL）或 ZnO（5、15 和 25 μg/mL）NP 共培养 96 h。TiO NP 被内化并聚集到细胞中，增加了卵泡直径并破坏了细胞骨架排列，这些作用部分被 trolox 共同暴露所阻止。此外，ZnO NP 部分溶解在培养基中，降低了卵泡直径，并破坏了细胞骨架排列，而 trolox 并不能阻止这些作用。暴露于两种 NP 引起的超微结构改变表现为跨带突起受损和线粒体肿胀。氧化应激介导了 TiO NP 诱导的效应，但不能介导 ZnO NP 诱导的效应，这表明在腔前卵泡发育过程中，两种 NP 诱导的毒性作用可能是通过不同的毒性机制引起的，这可能是由于 ZnO NP 的溶解度增加和 TiO NP 聚集到卵泡细胞中所致。
