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1. PAH-pollution effects on sensitive and resistant embryos: Integrating structure and function with gene expression

   https://doi.org/10.1371/journal.pone.0249432  

   Bozinovic, Goran; Shea, Damian; Feng, Zuying; Hinton, David; Sit, Tim; Oleksiak, Marjorie F. (April 2021, PLOS ONE)

   Cao, Yi (Ed.)

   Polycyclic aromatic hydrocarbons (PAHs) are among the most widespread natural and anthropogenic pollutants, and some PAHs are proven developmental toxicants. We chemically characterized clean and heavily polluted sites and exposed fish embryos to PAH polluted sediment extracts during four critical developmental stages. Embryos were collected from Fundulus heteroclitus populations inhabiting the clean and heavily polluted Superfund estuary. Embryos of parents from the clean sites are sensitive to PAH pollutants while those of parents from the heavily polluted site are resistant. Chemical analysis of embryos suggests PAH accumulation and pollution-induced toxicity among sensitive embryos during development that ultimately kills all sensitive embryos before hatching, while remarkably, the resistant embryos develop normally. The adverse effects on sensitive embryos are manifested as developmental delays, reduced heart rates, and severe heart, liver, and kidney morphological abnormalities. Gene expression analysis of early somitogenesis, heartbeat initiation, late organogenesis, and pre-hatching developmental stages reveals genes whose expression significantly differs between sensitive and resistant embryo populations and helps to explain mechanisms of sensitivity and resistance to polluted environments during vertebrate animal development. 

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

   https://doi.org/10.3390/ijms24076168  

   Wamucho, Anye; Unrine, Jason; May, John; Tsyusko, Olga (April 2023, International Journal of Molecular Sciences)

   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. 

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3. Epigenetic inheritance of DNA methylation changes in fish living in hydrogen sulfide–rich springs

   https://doi.org/10.1073/pnas.2014929118  

   Kelley, Joanna L.; Tobler, Michael; Beck, Daniel; Sadler-Riggleman, Ingrid; Quackenbush, Corey R.; Arias Rodriguez, Lenin; Skinner, Michael K. (June 2021, Proceedings of the National Academy of Sciences)

   Environmental factors can promote phenotypic variation through alterations in the epigenome and facilitate adaptation of an organism to the environment. Although hydrogen sulfide is toxic to most organisms, the fish Poecilia mexicana has adapted to survive in environments with high levels that exceed toxicity thresholds by orders of magnitude. Epigenetic changes in response to this environmental stressor were examined by assessing DNA methylation alterations in red blood cells, which are nucleated in fish. Males and females were sampled from sulfidic and nonsulfidic natural environments; individuals were also propagated for two generations in a nonsulfidic laboratory environment. We compared epimutations between the sexes as well as field and laboratory populations. For both the wild-caught (F0) and the laboratory-reared (F2) fish, comparing the sulfidic and nonsulfidic populations revealed evidence for significant differential DNA methylation regions (DMRs). More importantly, there was over 80% overlap in DMRs across generations, suggesting that the DMRs have stable generational inheritance in the absence of the sulfidic environment. This is an example of epigenetic generational stability after the removal of an environmental stressor. The DMR-associated genes were related to sulfur toxicity and metabolic processes. These findings suggest that adaptation of P. mexicana to sulfidic environments in southern Mexico may, in part, be promoted through epigenetic DNA methylation alterations that become stable and are inherited by subsequent generations independent of the environment. 

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4. Unraveling the Hsp70-ROS-autophagy axis in pentachlorophenol-challenged lung and liver epithelial cells

   https://doi.org/10.1007/s00204-025-03983-8  

   Thota, S; Begum, R; Mutyala, D; Bidarimath, N; Thakur, M; Sarkar, B; Morehouse, J; Yang, S; Deb, P K; Dorsey, W; et al (May 2025, Archives of Toxicology)

   Pentachlorophenol (PCP) was extensively utilized as an organochlorine pesticide and wood preservative in the United States from the 1930s until the Environmental Protection Agency (EPA) imposed restrictions due to concerns about its toxicity and potential carcinogenic properties. Although it is no longer widely used, PCP remains a concern due to its environmental persistence and potential for long-term health effects. Significant occupational and environmental exposures have likely occurred, with the health and economic costs of PCP exposure potentially being substantial given its known toxicity. Notably, PCP exhibits rapid absorption through both the skin and respiratory system and has been shown to cause hepatotoxicity, developmental toxicity, immunotoxicity, irritation, and carcinogenicity in laboratory animal studies. PCP exposure induces oxidative stress, a key mechanism underlying its inflammatory and toxic effects, which can activate cellular stress responses including upregulation of heat shock protein 70 (Hsp70). Previous studies in lung and liver epithelial cells have shown that Hsp70 and oxidative stress play pivotal roles in triggering autophagy. This study establishes the critical role of the Hsp70- reactive oxygen species (ROS)-autophagy axis in regulating cellular responses to PCP exposure in human alveolar (A549) and liver carcinoma (HepG2) epithelial cells. Our research elucidated the molecular mechanisms underlying PCP's cellular effects, demonstrating that its exposure resulted in increased expression of autophagy-related proteins (Beclin-1, LC3B, ATG12, and ATG16), subunits of NADPH oxidase (NCF-1, NCF-2, NOX2, and Rac), and antioxidant proteins (SOD and GPx) in both lung and liver cell types. Notably, PCP augmented the interaction between Hsp70 and the autophagy regulator Beclin-1. Pretreatment with the ROS inhibitor N-acetylcysteine or Hsp70 knockdown markedly reversed PCP-induced responses. Our in-silico protein–protein docking analysis and molecular dynamics simulation studies revealed enhanced interactions and/or stable confirmations maintained throughout the simulations for TLR4-Hsp70 and Hsp70-Beclin-1 complexes in the presence of PCP. These findings provide a strong foundation for future studies, employing in vivo experimental models and human populations to identify promising targets for PCP-induced toxicity and cellular injury. Furthermore, these findings may have far-reaching implications for public health and environmental policy, ultimately leading to the identification of biomarkers and the development of more effective interventions for environmentally induced toxicity and diseases. 

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5. Assessing the Role of Incubation Temperature as a Barrier to Successful Establishment of Coho Salmon ( Oncorhynchus kisutch ) in a Rapidly Warming Arctic

   https://doi.org/10.1002/ece3.70797  

   Lindley, Elizabeth D; Dunmall, Karen M; Westley, Peter_A H (January 2025, Ecology and evolution)

   ABSTRACT Warming associated with climate change is driving poleward shifts in the marine habitat of anadromous Pacific salmon (Oncorhynchusspp.). Yet the spawning locations for salmon to establish self‐sustaining populations and the consequences for the ecosystem if they should do so are unclear. Here, we explore the role of temperature‐dependent incubation survival and developmental phenology of coho salmon (Oncorhynchus kisutch) as a potential early life history barrier to establishment in an Arctic stream. We exposed embryos to temperatures previously recorded in the substrate of an Arctic groundwater spring‐fed spawning environment. Using a common garden experimental design, coho salmon embryos were exposed to treatments that thermally mimicked four spawning dates from August 1 to October 1 (AUG1, SEPT1, SEPT15, and OCT1). Spawning temperatures were 6°C at the warmest (AUG1) and 1.25°C at the coldest (OCT1). We observed low survival rates in SEPT1 (41%) and OCT1 (34%) and near complete mortality in the other treatments. While far below what is considered normal in benign hatchery‐like conditions, these rates suggest that temperatures experienced at these spawning dates are survivable. We detected differences in developmental rates across treatments; embryos developed 1.9 times faster in the warmest treatment (AUG1, 120 days) compared to the coldest (OCT1, 231 days). Differences in accumulated thermal units (ATUs) needed for hatching ranged from 392 ATUs in AUG1 to 270 ATUs in OCT1, revealing compensation in developmental requirements. Given these findings, the most thermally suitable spawning dates within our study are between September 15 and October 1, which facilitates hatching and projected nest emergence to occur in spring warming conditions (March–September). Broadly, our findings suggest that spawning sites within thermal tolerances that can support the survival and development of coho salmon exist in the North American Arctic. Whether the habitat is otherwise suitable for transitions through other life stages remains unknown. 

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