MicroRNA and Gut Microbiota Alter Intergenerational Effects of Paternal Exposure to Polyethylene Nanoplastics.
Jiaqi SunMiaomiao TengWentao ZhuXiaoli ZhaoLihui ZhaoYunxia LiZixuan ZhangYunjie LiuSheng BiFeng-Chang WuPublished in: ACS nano (2024)
Nanoplastics (NPs), as emerging contaminants, have been shown to cause testicular disorders in mammals. However, whether paternal inheritance effects on offspring health are involved in NP-induced reproductive toxicity remains unclear. In this study, we developed a mouse model where male mice were administered 200 nm polyethylene nanoparticles (PE-NPs) at a concentration of 2 mg/L through daily gavage for 35 days to evaluate the intergenerational effects of PE-NPs in an exclusive male-lineage transmission paradigm. We observed that paternal exposure to PE-NPs significantly affected growth phenotypes and sex hormone levels and induced histological damage in the testicular tissue of both F 0 and F 1 generations. In addition, consistent changes in sperm count, motility, abnormalities, and gene expression related to endoplasmic reticulum stress, sex hormone synthesis, and spermatogenesis were observed across paternal generations. The upregulation of microRNA (miR)-1983 and the downregulation of miR-122-5p, miR-5100, and miR-6240 were observed in both F 0 and F 1 mice, which may have been influenced by reproductive signaling pathways, as indicated by the RNA sequencing of testis tissues and quantitative real-time polymerase chain reaction findings. Furthermore, alterations in the gut microbiota and subsequent Spearman correlation analysis revealed that an increased abundance of Desulfovibrio (C21_c20) and Ruminococcus (gnavus) and a decreased abundance of Allobaculum were positively associated with spermatogenic dysfunction. These findings were validated in a fecal microbiota transplantation trial. Our results demonstrate that changes in miRNAs and the gut microbiota caused by paternal exposure to PE-NPs mediated intergenerational effects, providing deeper insights into mechanisms underlying the impact of paternal inheritance.
Keyphrases
- cell proliferation
- endoplasmic reticulum stress
- gene expression
- long non coding rna
- oxide nanoparticles
- signaling pathway
- oxidative stress
- single cell
- long noncoding rna
- diabetic rats
- mouse model
- high glucose
- induced apoptosis
- healthcare
- public health
- dna methylation
- mitochondrial dna
- clinical trial
- drug induced
- germ cell
- antibiotic resistance genes
- randomized controlled trial
- staphylococcus aureus
- high resolution
- metabolic syndrome
- mental health
- type diabetes
- escherichia coli
- risk assessment
- health information
- pseudomonas aeruginosa
- adipose tissue
- social media
- climate change
- phase ii
- mesenchymal stem cells
- mass spectrometry
- peripheral blood
- microbial community
- candida albicans
- human health