Iodoacetic acid exposure alters the transcriptome in mouse ovarian antral follicles

Iodoacetic acid(IAA) is an unregulated water disinfection byproduct that is an ovarian toxicant. However, the mechanisms of action underlying IAA toxicity in ovarian follicles remain unclear. Thus, we determined whether IAA alters gene expression in ovarian follicles in mice. Adult female mice were dosed with water or IAA(10 or 500 mg/L) in the water for 35-40 days. Antral follicles were collected for RNA-sequencing analysis and sera were collected to measure estradiol. RNA-sequencing analysis identified 1063 differentially expressed genes(DEGs) in the 10 and 500 mg/L IAA groups(false discovery rate FDR < 0.1), respectively, compared to controls. Gene Ontology Enrichment analysis showed that DEGs were involved with RNA processing and regulation of angiogenesis(10 mg/L) and the cell cycle and cell division(500 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the phosphatidylinositol 3-kinase and protein kinase B(PI3K-Akt), gonadotropin-releasing hormone(Gn RH), estrogen, and insulin signaling pathways(10 mg/L). Pathway Enrichment analysis showed that DEGs were involved in the oocyte meiosis, Gn RH, and oxytocin signaling pathways(500 mg/L). RNA-sequencing analysis identified 809 DEGs when comparing the 500 and 10 mg/L IAA groups(FDR < 0.1). DEGs were related to ribosome, translation, m RNA processing, oxidative phosphorylation, chromosome, cell cycle, cell division, protein folding, and the oxytocin signaling pathway. Moreover, IAA exposure significantly decreased estradiol levels(500 mg/L) compared to control. This study identified key candidate genes and pathways involved in IAA toxicity and can help to further understand the molecular mechanisms of IAA toxicity in ovarian follicles.

Effects of iodoacetic acid drinking water disinfection byproduct on the gut microbiota and its metabolism in rats

Iodoacetic acid(IAA) is an unregulated disinfection byproduct in drinking water and has been shown to exert cytotoxicity, genotoxicity, tumorigenicity, and reproductive and developmental toxicity. However, the effects of IAA on gut microbiota and its metabolism are still unknown, especially the association between gut microbiota and the metabolism and toxicity of IAA. In this study, female and male Sprague–Dawley rats were exposed to IAA at 0 and 16 mg/kg bw/day daily for 8 weeks by oral gavage. Results of 16S r RNA gene sequencing showed that IAA could alter the diversity, relative abundance and function of gut microbiota in female and male rats. IAA also increased the abundance of genes related to steroid hormone biosynthesis in the gut microbiota of male rats. Moreover, metabolomics profiling revealed that IAA could significantly disturb 6 and 13 metabolites in the feces of female and male rats, respectively. In female rats, the level of androstanediol increased in the IAA treatment group. These results were consistent with our previous findings, where IAA was identified as an androgen disruptor. Additionally, the perturbed gut microbiota and altered metabolites were correlated with each other. The results of this study indicated that IAA could disturb gut microbiota and its metabolism. These changes in gut microbiota and its metabolism were associated with the reproductive and developmental toxicity of IAA.

Functional evaluation of iodoacetic acid induced photoreceptor degeneration in the cat

Iodoacetic acid(IAA) has been applied to different species to acutely induce photoreceptor degeneration.The purpose of the present study was to use this toxin to thoroughly eliminate photoreceptors and induce complete blindness in the cat.IAA was delivered by single ear vein injection(20 mgkg-1).Six months after the IAA treatment,functional evaluations including pupillary light reflex(PLR),electroretinogram(ERG),visual behavior tests were performed.Morphological examinations were carried out after the functional evaluation.The present result shows that,six months after the IAA application,animals lost visual functions and became completely blind.High dose IAA application via ear vein delivery created an acute and reliable complete photoreceptor degeneration model in the cat.This model can be applied to genetic and cellular therapies for visual function restoration.

Relationships between regulated DBPs and emerging DBPs of health concern in U.S. drinking water

A survey was conducted at eight U.S. drinking water plants, that spanned a wide range of water qualities and treatment/disinfection practices. Plants that treated heavily-wastewaterimpacted source waters had lower trihalomethane to dihaloacetonitrile ratios due to the presence of more organic nitrogen and HAN precursors. As the bromide to total organic carbon ratio increased, there was more bromine incorporation into DBPs. This has been shown in other studies for THMs and selected emerging DBPs(HANs), whereas this study examined bromine incorporation for a wider group of emerging DBPs(haloacetaldehydes, halonitromethanes). Moreover, bromine incorporation into the emerging DBPs was, in general, similar to that of the THMs. Epidemiology studies that show an association between adverse health effects and brominated THMs may be due to the formation of brominated emerging DBPs of heath concern. Plants with higher free chlorine contact times before ammonia addition to form chloramines had less iodinated DBP formation in chloraminated distribution systems, where there was more oxidation of the iodide to iodate(a sink for the iodide) by the chlorine. This has been shown in many bench-scale studies(primarily for iodinated THMs), but seldom in full-scale studies(where this study also showed the impact on total organic iodine. Collectively, the THMs, haloacetic acids, and emerging DBPs accounted for a significant portion of the TOCl, TOBr, and TOI;however, ~50% of the TOCl and TOBr is still unknown. The correlation of the sum of detected DBPs with the TOCl and TOBr suggests that they can be used as reliable surrogates.