Global DNA Adenine Methylation in Caenorhabditis elegans after Multigenerational Exposure to Silver Nanoparticles and Silver Nitrate

Abstract

Multigenerational and transgenerational reproductive toxicity in a model nematode Caenorhabditis elegans has been shown previously after exposure to silver nanoparticles (Ag-NPs) and silver ions (AgNO3). However, there is a limited understanding on the transfer mechanism of the increased reproductive sensitivity to subsequent generations. This study examines changes in DNA methylation at epigenetic mark N6-methyl-2′-deoxyadenosine (6mdA) after multigenerational exposure of C. elegans to pristine and transformed-via-sulfidation Ag-NPs and AgNO3. Levels of 6mdA were measured as 6mdA/dA ratios prior to C. elegans exposure (F0) after two generations of exposure (F2) and two generations of rescue (F4) using high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Although both AgNO3 and Ag-NPs induced multigenerational reproductive toxicity, only AgNO3 exposure caused a significant increase in global 6mdA levels after exposures (F2). However, after two generations of rescue (F4), the 6mdA levels in AgNO3 treatment returned to F0 levels, suggesting other epigenetic modifications may be also involved. No significant changes in global DNA methylation levels were observed after exposure to pristine and sulfidized sAg-NPs. This study demonstrates the involvement of an epigenetic mark in AgNO3 reproductive toxicity and suggests that AgNO3 and Ag-NPs may have different toxicity mechanisms.

Multigenerational Effects of Graphene Oxide Nanoparticles on Acheta domesticus DNA Stability

“…However, when the nematodes were intoxicated with AgNO 3 , an increase in global DNA methylation was detected. This led the authors to hypothesize the existence of different epigenetic marks for AgNPs and AgNO 3 [ 31 ].…”

“…To date, the vast majority of published findings have focused on the multigenerational imprint of NPs on developmental and reproductive parameters [ 21 , 22 , 23 , 24 , 25 , 26 ]. However, limited attention has been given to studying the multigenerational effects of GO treatment, including oxidative DNA damage and epigenetic changes [ 15 , 27 , 28 , 29 , 30 , 31 , 32 , 33 ]. In a study by Wang and Liu [ 15 ], the transgenerational effects of silver NPs on the gastropod L. stagnalis were investigated.…”

N6-Methyladenine Progressively Accumulates in Mitochondrial DNA during Aging

“…DNA methylation at the N 6 position of adenine is the other major type of epigenetic modification, which has been widely recognized in bacteria and plants [9,10]. A few years ago, DNA 6mA modification was also identified in the genome of a diverse range of animal taxa ranging from worms to mammals [11][12][13][14][15]. Furthermore, the presence of 6mA was recently detected in mammalian mtDNA [16].…”

Evaluation of the Reproductive Toxicity of Fluopimomide in Meloidogyne incognita and Caenorhabditis elegans

“…Yu et al [21] employed C. elegans to determine the effect of long-term plastic pollution on reproductive toxicity, which found that a single long-term maternal nanoplastics exposure caused multiand trans-generational reproduction decline in the nematodes. In addition, indicators such as brood size, DNA damage, and cell apoptosis are also widely used in reproductive research [22,23]. It is still unknown whether fluopimomide has effects on DNA damage and cell apoptosis in C. elegans.…”