Multigenerational reproduction and developmental toxicity, and HPG axis gene expression study on environmentally-relevant concentrations of nonylphenol in zebrafish.

Nonylphenol (NP) is a toxic xenobiotic compound, which is persistent in the aquatic environment and is extremely toxic to aquatic organisms. Although the exact molecular mechanisms of its toxic effect are well understood, the multigenerational reproduction and multigenerational - gene expression changes caused by NP still remain unclear. The following work investigated the effect of NP on four consecutive generations of zebrafish by examining their growth and several reproductive parameters, the degree of gonad damage, and the expression of related reproduction related genes. The results showed that high concentrations (20 and 200 μg·L) of NP could decrease growth and induce gonad damage in zebrafish. In addition, gnrh2 and gnrh3 genes were up-regulated, and fshβ and lhβ genes were downregulated in the hypothalamus in male zebrafish; while in female fish, the fshβ and lhβ were upregulated in P and F1 generations, and then down-regulated in the F2 generation. Meanwhile, the cyp19a1a gene was downregulated in the gonad of male fish, while the genes of fshr, lhr and esr showed a downward trend in females. Compared to P generation, F2 generation was more tolerant to higher NP concentrations (20 and 200 μg·L), as was also more sensitive to lower concentrations of NP (2 μg·L). Consequently, stress and damage caused by environmentally-relevant concentrations of aquatic pollutants in a vertebrate model were measured and predicted. Prevention and control measures can be actively and effectively proposed, which might be transversal to other exposed organisms, including humans. After several generations, typical transgenerational genetic phenomena might occur, which should be addressed by further studies.