Titanium dioxide (TiO₂) 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 TiO₂ 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 TiO₂ and ZnO NP induce oxidative stress, thus this study indirectly assessed whether oxidative stress was involved. Antral follicles were cultured with TiO₂ (5, 25 and 50 μg/mL) or ZnO (5, 15 and 25 μg/mL) NP for 96 h. TiO₂ 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 TiO₂ 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 TiO₂ NP into the follicular cells.

二氧化钛 (TiO ₂ ) 和氧化锌 (ZnO) 纳米粒子 (NP) 已被证明可以到达卵巢。然而，这些金属基 NP 对卵巢窦卵泡的潜在有害影响以及它们是否可以被卵泡细胞直接吸收尚不清楚。本研究的目的是评估 TiO ₂和 ZnO NP 是否内化到窦卵泡中，并进一步比较了任何一种 NP 对窦卵泡生长、超微结构和活力的任何潜在有害影响。已经描述了TiO ₂和ZnO NP诱导氧化应激，因此本研究间接评估了是否涉及氧化应激。用 TiO _{2培养窦卵泡}（5、25 和 50 μg/mL）或 ZnO（5、15 和 25 μg/mL）NP 96 小时。TiO ₂ 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，与 trolox 的共同暴露部分阻止了这些影响。此外，ZnO NP 部分溶解到培养基中，减少了卵泡直径，破坏了细胞骨架排列，而 trolox 无法阻止这些影响。暴露于两种 NP 引起的超微结构改变由受损的跨带投射和肿胀的线粒体证明。氧化应激介导 TiO ₂NP 诱导的效应，但不是 ZnO NP 在窦卵泡发育中的效应。我们的研究结果表明，两种 NP 通过不同的毒性机制诱导卵巢卵泡毒性，可能是由于 ZnO NP 溶解度的刺激和 TiO ₂ NP 聚集到卵泡细胞中。