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

Zhai, Qiu-Yue; Ge, Wei; Wang, Junjie; Sun, Xiao‐Feng; Ma, Jin-Mei; Liu, Jing-Cai; Zhao, Yong; Feng, Yanzhong; Dyce, Paul W.; Felici, Massimo De; Shen, Wei

doi:10.18632/aging.101539

Cited by 31 publications

(13 citation statements)

References 52 publications

(58 reference statements)

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“…In this study, a TUNEL BrightGreen Apoptosis Detection Kit (Vazyme, Nanjing, China, A112) was used for TUNEL staining experiments 68 . After secondary antibody incubation was completed according to the immunofluorescence protocol, proteinase K was used for incubation at RT for 15 min.…”

Section: Methodsmentioning

confidence: 99%

Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

et al. 2021

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Rationale: Zearalenone (ZEN), a pollutant in our daily diet, seriously threatens the reproductive health of humans and animals. The primordial follicle (PF) assembly in the mouse occurs during the perinatal period, which determines the whole ovarian reserve in reproductive lifespan. In the current investigation, we administered ZEN orally to perinatal mice from 16.5 days post coitum (dpc) to postnatal day 3 (PD3), and single-cell RNA sequencing (scRNA-seq) was performed on PD0 and PD3 ovarian tissues in the offspring to check ZEN toxic to primordial follicle formation at the single cell level. Methods: Ovarian tissues ( in vivo ) were examined by single cell RNA sequencing analysis, Immunostaining, and Western blotting. Ovarian tissues ( in vitro ) were examined by qRT-PCR, Immunostaining, and Western blotting. Results: We found that ZEN exposure altered the developmental trajectory of both germ cells and granulosa cells. Furthermore, after establishing the cell-cell communication network between germ cells and granulosa cells, we found that this was perturbed by ZEN exposure, especially during the Hippo signaling pathway. Conclusions: This study showed that ZEN affected the status of germ cells and granulosa cells through the Hippo signaling pathway and blocked the assembly of PFs. This research contributes to our deeper understanding of the mechanisms of toxicity in different cell types and the disruption of normal intercellular signaling by ZEN exposure.

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Section: Methodsmentioning

confidence: 99%

Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

et al. 2021

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“…In addition, NPs may penetrate the blood‐testis barrier and display adverse effects on testis, or NPs may be internalized in ovarian granulosa cells and relocate in the uterus and cause reproductive toxicity. Compared with ZnSO4 and bulk ZnO, ZnO NPs could pass though cell membrane and accumulate within the oocyte cytoplasm, which induced DNA damage and adversely impact pachytene oocytes in fetal ovaries 14 . Mozaffari et al suggested that ZnO NPs induce significant changes in testis tissue and show destructive effects on spermatogenesis 15 .…”

Section: Introductionmentioning

confidence: 99%

“…Compared with ZnSO4 and bulk ZnO, ZnO NPs could pass though cell membrane and accumulate within the oocyte cytoplasm, which induced DNA damage and adversely impact pachytene oocytes in fetal ovaries. 14 Mozaffari The present study aimed to establish the possible reproductive effects and the gene expression profiles following an oral, short-term (3 days) exposure to ZnO NPs in female and male mice. To assess this, histopathological changes and the gene expression involved in immune/inflammation responses, apoptosis, oxidative stress, the metabolic process, and sex hormone associated genes were investigated.…”

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confidence: 99%

Reproductive organ dysfunction and gene expression after orally administration of ZnO nanoparticles in murine

Kuang

Zhang

Yang

et al. 2020

Environmental Toxicology

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ZnO nanoparticles (NPs) are among the most manufactured nanoparticles in the consumer products, industries, and researches. An increasing body of evidence indicated that ZnO NPs show toxicological effects in vivo. Sex differences in the toxicity of ZnO NPs are not clear, thus the aim of this study was to investigate the effects of ZnO NPs on the female and male reproductive organs (uterus, ovary and testes). ZnO NPs were orally administered to female and male mice at dosages level of 0 and 100 mg/kg body weight. The biological material was sampled 3 days after tube feeding. The results demonstrated that Zinc contents were accumulated in the reproductive organs of treated mice. Furthermore, ZnO NPs administration induced significant decrease in the testes weight, an imbalance of hematological and serum biochemical parameters in male mice. The histopathological examinations showed that structural disorder and the appearance of cell apoptosis and death in the ZnO NPs‐exposed mice. Additionally, the RT‐qPCR data indicated ZnO NPs can activate mitochondrial‐mediated signaling pathway and induce caspase depend damage that ultimately injured the uterus. In the ovary, ZnO NPs induce cell apoptosis in Shh pathway activated ovary cells, and affect the synthesis of steroidogenesis. In the testes, ZnO NPs effectively changed the expression level of genes related to oxidant stress, detox/metabolic process, and apoptosis. It was found that ZnO NPs caused more serious reproductive toxicity in the male mice than female mice. Overall, these findings indicated that ZnO NPs could induce exposure‐related risks to reproductive health, especially in those who are at the occupational level.

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“…In mice, PGCs at embryonic day 13.5 (E13.5) enter into the prophase I of meiotic divisions and subsequently they are arrested at the diplotene stage of prophase I of meiosis. Failure to properly shape and repair meiotic double‐stranded DNA (DSBs) results in gametes with chromosome structural alterations or aneuploidy, which can cause developmental disorders (Zhai et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

The effect of different concentrations of cerium oxide during pregnancy on ovarian follicle development in neonatal mice

Nemati

Beyranvand

Assadollahi

et al. 2020

Birth Defects Research

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Objectives Cerium is a member of the rare metals group and widely used in drug delivery, gene therapy, molecular imaging and medicine. In this study, we investigated the effect of different doses of Cerium (IV) oxide (CeO2) during pregnancy on neonatal mice ovaries, as well as its effect on blood biochemical parameters. Methods Thirty pregnant NMRI mice were divided into five groups: Control and 4 groups treated with CeO2 (10, 25, 80, 250 mg/kg.bw i.p) at the GD7 and GD14. The ovarian histological of neonatal (2 and 6 day‐olds), as well as blood serum of neonates at 15‐dpp were analyzed. Results Count of ovarian primordial follicles in neonates at 2 dpp showed a significant decrease in the groups treated with 80 and 250 mg/kg.bw doses of CeO2. There was also a significant decrease in ovarian primordial and primary follicles in neonates at 6‐dpp at 250 mg/kg.bw doses of CeO2 in the control (P < 0.05). There was no significant difference in serum levels of malondialdehyde and total antioxidant capacity between the experimental and control groups. Conclusions Our results suggest that the effects of CeO2 on the ovarian tissue of neonatal mice during pregnancy may be dose‐dependent.

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

Cited by 31 publications

References 52 publications

Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

Single-cell transcriptomic profiling provides insights into the toxic effects of Zearalenone exposure on primordial follicle assembly

Reproductive organ dysfunction and gene expression after orally administration of ZnO nanoparticles in murine

The effect of different concentrations of cerium oxide during pregnancy on ovarian follicle development in neonatal mice

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