Abstract
Chitosan nanoparticles (CSNPs) are used as drug or gene delivery vehicles. However, a detailed understanding of the effects of CSNPs on embryonic development remains obscure. Here, we show that CSNPs can be internalized into mouse blastocysts, such as the zona pellucida, the perivitelline space, and the cytoplasm. Consequently, CSNPs-induced endoplasmic reticulum (ER) stress increases both of Bip/Grp78, Chop, Atf4, Perk, and Ire1a mRNAs expression levels, and reactive oxygen species. Moreover, CSNPs show double- and multi-membraned autophagic vesicles, and lead to cell death of blastocoels. Conversely, treatment with rapamycin, which plays an important role as a central regulator of cellular proliferation and stress responses, decreased CSNPs-induced mitochondrial Ca+2 overloading, apoptosis, oxidative stress, ER stress, and autophagy. In vivo studies demonstrated that CSNPs injection has significant toxic effect on primordial and developing follicles. Notably, rapamycin rescued oxidative stress-induced embryonic defects via modulating gene expression of sirtuin and mammalian target of rapamycin. Interestingly, CSNPs treatment alters epigenetic reprogramming in mouse embryos. Overall, these observations suggest that rapamycin treatment could ameliorate CSNPs-induced developmental defects in preimplantation embryos. The data from this study would facilitate to understand the toxicity of these CSNPs, and enable the engineering of safer nanomaterials for therapeutic applications.
Highlights
Nanotechnology is a key technology that plays an important role in various disciplines, such as electronics, the optical industry, environmental engineering, biotechnology, and nanomedicines [1,2,3,4]
We examined the interaction of chitosan nanoparticles (CSNPs) with preimplantation embryos and the activation of various genes involved in embryonic physiological processes
The embryos treated with CSNPs showed severely swollen mitochondria, autophagosomes, lipid droplets, and lysosomes were the predominant types of autophagic vacuoles (Figure S1), indicating that removing the damaged mitochondria and the accumulated lipid droplets is most pertinent for protecting host cells from CSNPs-induced injury
Summary
Nanotechnology is a key technology that plays an important role in various disciplines, such as electronics, the optical industry, environmental engineering, biotechnology, and nanomedicines [1,2,3,4]. It is very well known that chitosan nanoparticles (CSNPs) are nontoxic, biodegradable polycationic polymers with low immunogenicity [5]. Previous studies have shown that CSNPs are cytotoxic to tumor cell lines [6]. Loh et al [7] found that CSNPs could be internalized by human liver cells, reducing the cell’s viability and proliferation and compromising the integrity of the cell membrane. Titanium dioxide nanoparticles (TiO2 NPs) can accumulate in the ovaries, and this accumulation results in ovarian damage, causes an imbalance in the distribution of mineral elements and sex hormones, decreases fertility, and causes oxidative stress in mice [8]. The daily inhalation of cadmium oxide nanoparticles (CdO NPs, 230μg/m3) increased the uterine weight and altered the placental weight of pregnant CD-1 mice [9].
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