The Invasion and Reproductive Toxicity of QDs-Transferrin Bioconjugates on Preantral Follicle in vitro

Abstract

The toxicity of QD has been extensively studied over the past decade. However, the potential toxicity of QDs impedes its use for clinical research. In this work, we established a preantral follicle in vitro culture system to investigate the effects of QD-Transferrin (QDs-Tf) bioconjugates on follicle development and oocyte maturation. The preantral follicles were cultured and exposed to CdTe/ZnTe QDs-Tf bioconjugates with various concentrations and the reproductive toxicity was assessed at different time points post-treatment. The invasion of QDs-Tf for oocytes was verified by laser scanning confocal microscope. Steroid production was evaluated by immunoassay. C-band Giemsa staining was performed to observe the chromosome abnormality of oocytes. The results showed that the QDs-Tf bioconjugates could permeate into granulosa cells and theca cells, but not into oocyte. There are no obvious changes of oocyte diameter, the mucification of cumulus-oocyte-complexes and the occurrence of aneulpoidy as compared with the control group. However, delay in the antrum formation and decrease in the ratio of oocytes with first polar body were observed in QDs-Tf-treated groups. The matured oocytes with first polar body decreased significantly by ~16% (from 79.6±10 % to 63±2.9 %) when the concentration of QDs-Tf bioconjugates exceeded 2.89 nmol·L-1 (P < 0.05). Our results implied that the CdTe/ZnTe QDs-Tf bioconjugates were reproductive toxic for follicle development, and thus also revealed that this in vitro culture system of preantral follicle is a highly sensitive tool for study on the reproductive toxicity of nanoparticles.

The Reproductive Toxicity of CdSe/ZnS Quantum Dots on the in vivo Ovarian Function and in vitro Fertilization

“…They reported that the nanoparticles perturbed the mitochondrial membranes of granulosa cells, and eventually affected the steroidogenesis via an oxidative stress-mediated mechanism. Our previous work also confirmed that the QDs could be uptaken by granulosa cells and theca cells in vitro 1931.…”

“…In the first case, the oocyte with immatured cytoplasm contained in COCs will decrease the in vitro fertilization. The oocyte maturation includes nuclear maturation and cytoplasmic maturation19. The oocyte nucleus maturation characterizes with a released first polar body.…”

“…For reproductive toxicity study on QDs, the preantral follicle in vitro growth system had been demonstrated to be 10 times more sensitive than the conventional in vivo animals for reproductive medical and biological investigations1939, the lack of in vivo environment and the coordination of pituitary, ovary and hypothalamus will lead to inconclusive judgement, especially for hormones-relevant studies. The in vivo mammals provided an actual ovarian environment for regulating the maturation of oocytes2040.…”

“…In our previous study, we have co-cultured CdSe/CdS/ZnS QDs with immature oocytes or preantral follicles in vitro whereby the observation was on the invasion of QDs and the development of oocytes1819. We found that the QDs were not able to transmigrate into the zona pellucida and thereby entered the oocyte.…”

Reprotoxicité des nanoparticules

“…Plusieurs é tudes in vitro sur la reprotoxicité des quantum dots ont é té mené es sur des cellules folliculaires ou des ovocytes murins. En 2012, Xu et al [68], ont montré que des QDs conjugué s à la transferrine affectaient la maturation ovocytaire en s'accumulant dans les cellules de la granulosa (mais pas dans l'ovocyte), interfé raient avec le processus de maturation ovocytaire et perturbaient le signal entre les cellules germinales et les cellules somatiques gonadiques. L'é quipe de Wang [69] a é galement retrouvé une diminution du taux d'ovocytes matures dans les follicules exposé s in vitro par rapport aux contrô les non exposé s et une accumulation des QDs dans les cellules folliculaires.…”