Dataset Information

Two-generational impacts of airway exposure to silver nanoparticles in utero on male reproductive function in mice

ABSTRACT: This study investigated the effects of airway exposure to silver nanoparticles (AgNPs) in utero on male reproductive function. Exposure of pregnant ICR mice to AgNPs (low dose: 5 μg/injection; high dose: 50 μg/injection) at embryonic day 7.5 and 14.5, by means of intratracheal administration, resulted in dose-dependent exacerbation of sperm parameters in both F1 and F2 males. Microarray analysis revealed that the high-dose group displayed significant upregulation of four microRNAs (miRNAs) and downregulation of seven miRNAs, as compared to the control group, results that were further verified using quantitative real-time PCR. Interestingly, in the mature sperm as well, the high-dose group displayed significant upregulation of one, and downregulation of three of the miRNAs found to be dysregulated in the testes. Notably, in silico analyses predicted that the target genes of the differentially expressed miRNAs in the sperm were significantly associated with neuronal development. Neuronal migration in the cerebral cortex was dysregulated in the F2 males, accompanied by depression-like behavior. These observations demonstrated for the first time that prenatal exposure to AgNPs can induce germ cell development dysfunction in F1 males, which is involved in developmental toxicity in F2 males born to those F1 males.

ORGANISM(S): Mus musculus synthetic construct

PROVIDER: GSE245433 | GEO | 2025/07/30

REPOSITORIES: GEO

ACCESS DATA

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Project description:Background: DNA methylation (DNAme) erasure and reacquisition occurs during prenatal male germ cell development; some further remodelling takes place after birth during spermatogenesis. Environmental insults during germline epigenetic reprogramming may affect DNAme, presenting a potential mechanism for transmission of environmental exposures across multiple generations. Objectives: We investigated how germ cell DNAme is impacted by lifetime exposures to diets containing either low or high, clinically relevant, levels of the methyl donor folic acid and whether resulting DNAme alterations were inherited in germ cells of male offspring of subsequent generations. Materials and Methods: Female mice were placed on a 7-fold folic acid deficient (7FD) and 10- or 20-fold supplemented (10FS and 20FS) diets before and during pregnancy. Resulting F1 litters were weaned on the respective diets. F2 and F3 males received control diets. Genome-wide DNAme was assessed in F1 spermatogonia, and in F1, F2 and F3 sperm. Results: In F1 germ cells, a greater number of differentially methylated cytosines (DMCs) was observed in spermatogonia as compared with F1 sperm for all folic acid diets. DMCs were lower in number in F2 versus F1 sperm, while an unexpected increase was found in F3 sperm. DMCs were predominantly hypomethylated, with genes in neurodevelopmental pathways commonly affected in F1, F2 and F3 male germ cells. While no DMCs were found to be inherited inter- or transgenerationally, we observed over-representation of repetitive elements, particularly young LINEs. Discussion and Conclusion: These results suggest that the prenatal window is the time most susceptible to folate-induced alterations in sperm DNAme in male germ cells. Altered methylation of specific sites in F1 sperm was not present in later generations. However, the finding of hypomethylated young LINE1 elements in sperm from F1 to F3 males provides insight into potential mechanisms of epigenetic inheritance of the effects of folate deficiency and supplementation.

Dataset Information

Two-generational impacts of airway exposure to silver nanoparticles in utero on male reproductive function in mice

Dataset's files

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets