Safe-by-design nanoparticles show reduced risk for female fertility

Antonella CAMAIONI, University of Rome Tor-Vergata  

Metal oxide nanoparticles (NPs) are increasingly used for industrial and biomedical applications, however their impact on occupational and public health is widely debated. Over the last years, interest on the effect of nanoparticle exposure on fertility has emerged, and safe-by-design approaches represent the answer for safety concerns. In this respect, we have studied the effect of four types of ZnO NPs on oocyte maturation and cumulus expansion, in vitro. Two of the tested ZnO NPs were obtained from JRC (NM-110 and NM-111) and had a crystal size of 42 nm and 34 nm, respectively; NM-111 was characterized by the presence of triethoxycaprylsilane coating. The other two ZnO NPs were in house prepared, and were pure or silica coated, with a crystal size of 30 nm, and a 5 nm silica coating. Cumulus cell-oocyte complexes (COCs) from pre-ovulatory follicles, obtained from 21-22 day old pre-pubertal mice, were cultured for 16-18h in the presence of various concentrations of the tested NPs (0.1-200 µg/ml). The ability of COCs to expand following the organization of a muco-elastic extracellular matrix and of the oocyte to re-enter meiosis were recorded. Trypan blue staining was performed to evaluate cell viability. Ability of the four different NPs to modulate the expression of genes involved in COCs maturation was studied.  Our results showed that COCs maturation, and related gene expression, was affected by the presence of ZnO NPs. The presence of a coating was able to reduce toxicity, suggesting that the negative effect of ZnO NPs on female fertility might be related to the release of Zn ions, known to be involved in follicular maturation. Most likely, the silica coating, better than the triethoxycaprylsilane coating, was able to prevent the ion release.

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