Endocrine disruption by several aniline derivatives and related mechanisms in a human adrenal H295R cell line and adult male zebrafish

Aniline and aniline derivatives have been widely used in the production of pesticides, pharmaceuticals, cosmetic, dyes, rubber, and adhesives products. These chemicals can easily be released into the environment through industrial and municipal discharges or as degradation byproducts. Several studies have suggested that aniline and some of its derivatives could cause reproductive toxicity in aquatic organisms. However, knowledge on the endocrine disruption potentials of these chemicals is limited only to aniline and associated mechanisms are rarely investigated. The objective of this study was to investigate the potential of major aniline derivatives, i.e., 3,4-dichloroaniline (3,4-DCA), 1-naphthylamine (1-NPA), and 4,4'-methylenedianiline (4,4'-MDA), to disrupt sex steroid production and other biological processes. For this purpose, the human adrenal H295R cell line and adult male zebrafish (Danio rerio) were used. In the H295R cell line, all tested aniline derivatives decreased testosterone (T) levels. Regulatory changes of several steroidogenic genes, i.e., down-regulation of StAR or CYP17 genes, and up-regulation of CYP19A, observed in the H295R cells could explain the sex hormone disruption. In male zebrafish, generally similar directions of changes, i.e., decreases in T levels and increased E2/T ratios, were observed. Again, down-regulation of key steroidogenic genes such as cyp17 or 3β-hsd, but slight up-regulation of cyp19a gene observed in the fish could explain the sex hormone changes. The results of our study demonstrate that all tested aniline derivatives could influence steroidogenesis and disrupt sex hormone balance toward reduced androgenicity. Consequences of anti-androgenicity following long-term exposure warrant further investigation.