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Updated: Aug 17, 2025
Using Caenorhabditis elegans for Studying Trans- and Multi-Generational Effects of Toxicants
Published on: July 29, 2019
Transgenerational bone toxicity in F3 medaka (Oryzias latipes) induced by ancestral benzo[a]pyrene exposure: Cellular
Jiezhang Mo1, Miles Teng Wan2, Doris Wai-Ting Au3
1Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 510000, China; Shenzhen Key Laboratory for the Sustainable Use of Marine Biodiversity, Research Centre for the Oceans and Human Health, Shenzhen Research Institute, City University of Hong Kong, Shenzhen 518057, China; State Key Laboratory of Marine Pollution and Department of Chemistry, City University of Hong Kong, Hong Kong SAR, China.
Abstract:
Benzo[a]pyrene (BaP), a ubiquitous pollutant, raises environmental health concerns due to induction of bone toxicity in the unexposed offspring. Exposure of F0 ancestor medaka (Oryzias latipes) to 1 µg/L BaP for 21 days causes reduced vertebral bone thickness in the unexposed F3 male offspring. To reveal the inherited modifications, osteoblast (OB) abundance and molecular signaling pathways of transgenerational BaP-induced bone thinning were assessed. Histomorphometric analysis showed a reduction in OB abundance. Analyses of the miRNA and mRNA transcriptomes revealed the dysregulation of Wnt signaling (frzb/ola-miR-1-3p, sfrp5/ola-miR-96-5p/miR-455-5p) and bone morphogenetic protein (Bmp) signaling (bmp3/ola-miR-96-5p/miR-181b-5p/miR-199a-5p/miR-205-5p/miR-455-5p). Both pathways are major indicators of impaired bone formation, while the altered Rank signaling in osteoclasts (c-fos/miR-205-5p) suggests a potentially augmented bone resorption. Interestingly, a typical BaP-responsive pathway, the Nrf2-mediated oxidative stress response (gst/ola-miR-181b-5p/miR-199a-5p/miR-205), was also affected. Moreover, mRNA levels of epigenetic modification enzymes (e.g., hdac6, hdac7, kdm5b) were found dysregulated. The findings indicated that epigenetic factors (e.g., miRNAs, histone modifications) may directly regulate the expression of genes associated with transgenerational BaP bone toxicity and warrants further studies. The identified candidate genes and miRNAs may serve as potential biomarkers for BaP-induced bone disease and as indicators of historic exposures in wild fish for conservation purposes.
