Differential Regulation of Gene and Protein Expression by Zinc Oxide Nanoparticles in Hen’s Ovarian Granulosa Cells: Specific Roles of Nanoparticles

Abstract

Annually, tons and tons of zinc oxide nanoparticles (ZnO NPs) are produced in the world. And they are applied in almost all aspects of our life. Their release from the products into environment may pose issue for human health. Although many studies have reported the adverse effects of ZnO NPs on organisms, little is known about the effects on female reproductive systems or the related mechanisms. Quantitative proteomics have not been applied although quantitative transcriptomics have been used in zinc oxide nanoparticles (ZnO NPs) research. Genes are very important players however proteins are the real actors in the biological systems. By using hen’s ovarian granulosa cells, it was found that ZnO-NP-5μg/ml and ZnSO4-10μg/ml treatments produced the same amount of intracellular Zn and resulted in similar cell growth inhibition. And NPs were found in the treated cells. However, ZnO-NP-5μg/ml specifically regulated the expression of genes and proteins compared with that in ZnSO4-10μg/ml treatment. For the first time, this investigation reports that intact NPs produce different impacts on the expression of genes and proteins involved in specific pathways compared to that by Zn2+. The findings enrich our knowledge for the molecular insights of zinc oxide nanoparticles effects on the female reproductive systems. This also may raise the health concern that ZnO NPs may adversely affect the female reproductive systems through regulation of specific signaling pathways.

Mass spectrometry-based proteomics for system-level characterization of biological responses to engineered nanomaterials

“…Omics-based approaches such as transcriptomics have been applied extensively for profiling gene expression changes upon ENM exposure [25,27–30]. Although these studies provide valuable information on how ENMs alter gene expression, the changes at the mRNA level do not necessarily correlate with changes at the protein level.…”

Exposure to Zinc oxide nanoparticles during pregnancy induces oocyte DNA damage and affects ovarian reserve of mouse offspring

“…They are heavily used due to their unique characteristics, such as high hydrophilicity, and ease of synthesis [ 21 , 22 ]. The increasing use of nanomaterials has raised concerns about the potential risks to human health, especially on the reproduction system [ 5 , 23 , 24 ]. Several studies have addressed the concerns of NPs exposure on reproductive health, however these studies focused on the impact of NPs on germ cell and pregnancy complications [ 5 , 20 , 25 ] ( Figure 7 ).…”

Regulation of MicroRNAs, and the Correlations of MicroRNAs and Their Targeted Genes by Zinc Oxide Nanoparticles in Ovarian Granulosa Cells

“…The methods for characterization of ZnO NPs were just published in our previous paper [ 41 ]. ZnO NPs were synthesized by Beijing DK nano technology Co. LTD (Beijing, P. R. China).…”

“…By reinforcing transcriptional programs and attenuating aberrant transcripts, microRNAs help to confer robustness to biological processes [ 40 ]. ZnO NPs have been reported to result in adverse effect on organisms and to change the expression of genes related to cytoskeletal transport, cellular respiration, and reproduction in Daphnia magna [ 16 ], and in our recent study we found ZnO NPs regulate the protein expression too [ 41 ]. Do microRNAs buffer against the variation in gene expression caused by ZnO NPs?…”

“…As descripted in our previous publication, ovarian granulosa cells of chicken and mammals are similarly steroidogenic hormone production cells and play very important roles in oocyte development and early embryogenesis because they are the closest cells to germ cells and they transport nutrition and produce other factors for oocyte growth [ 41 – 44 ]. Further, our research focus was female reproductive toxicology.…”