Silica encapsulation of ZnO nanoparticles reduces their toxicity for cumulus cell-oocyte-complex expansion

Antonella Camaioni,Micol Massimiani,Anna Pino,Manuel Scimeca,Valentina Lacconi,Flemming R Cassee,Luisa Campagnolo,Elena Bonanno,Flavia Barone,Ivo Iavicoli,Antonio Pietroiusti,Antonietta Salustri,Philip Demokritou,Dimitrios Bitounis,Valentina Prota,Georgios A Sotiriou,Andrea Magrini,Dilpreet Singh,Beatrice Bocca

doi:10.1186/s12989-021-00424-z

Abstract

BackgroundMetal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, hence their impact on occupational and public health has become a concern. In recent years, interest on the effect that exposure to NPs may exert on human reproduction has grown, however data are still scant. In the present work, we investigated whether different metal oxide NPs interfere with mouse cumulus cell-oocyte complex (COC) expansion.MethodsMouse COCs from pre-ovulatory follicles were cultured in vitro in the presence of various concentrations of two types of TiO2 NPs (JRC NM-103 and NM-104) and four types of ZnO NPs (JRC NM-110, NM-111, and in-house prepared uncoated and SiO2-coated NPs) and the organization of a muco-elastic extracellular matrix by cumulus cells during the process named cumulus expansion was investigated.ResultsWe show that COC expansion was not affected by the presence of both types of TiO2 NPs at all tested doses, while ZnO NM-110 and NM-111 induced strong toxicity and inhibited COCs expansion at relatively low concentration. Medium conditioned by these NPs showed lower toxicity, suggesting that, beside ion release, inhibition of COC expansion also depends on NPs per se. To further elucidate this, we compared COC expansion in the presence of uncoated or SiO2-coated NPs. Differently from the uncoated NPs, SiO2-coated NPs underwent slower dissolution, were not internalized by the cells, and showed an overall lower toxicity. Gene expression analysis demonstrated that ZnO NPs, but not SiO2-coated ZnO NPs, affected the expression of genes fundamental for COC expansion. Dosimetry analysis revealed that the delivered-to-cell mass fractions for both NPs was very low.ConclusionsAltogether, these results suggest that chemical composition, dissolution, and cell internalization are all responsible for the adverse effects of the tested NPs and support the importance of a tailored, safer-by-design production of NPs to reduce toxicity.

Highlights

Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, their impact on occupational and public health has become a concern
SiO2-coated zinc oxide NP (NP) synthesis and characterization The TiO2 NPs used in this study were rutile TiO2 NM103 and NM-104 obtained from the Repository for Representative Test Materials of the European Commission Joint Research Centre (JRC)
Trasmission electron microscope (TEM) analysis allowed defining the size of both types of particles, which was in the range of 22– 26 ± 10 nm, and identified that both NP powders were highly aggregated, with aggregates in the size range of 20–500 nm

Summary

Introduction

Metal oxide nanoparticles (NPs) are increasingly used in many industrial and biomedical applications, their impact on occupational and public health has become a concern. During the final stages of follicle growth preceding ovulation, vascular permeability increases, permitting the access of even large serum components [12] that, together with cumulus and oocyte products, allows the proper formation of follicular fluid that accumulates between cells and fills the antrum, the central cavity of Graafian preovulatory follicle. This physiological process may allow the arrival of potentially toxic substances present in blood close to the oocytes [13, 14]. The above mentioned in vitro models were designed to test either oocyte maturation or both COC expansion and oocyte maturation

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