In utero exposure to environmentally relevant concentrations of PCB 153 and PCB 118 disrupts fetal testis development in sheep.

Polychlorinated biphenyls (PCB) are environmental pollutants linked to adverse health effects including endocrine disruption and disturbance of reproductive development. This study aimed to determine whether exposure of pregnant sheep to three different mixtures of PCB 153 and PCB 118 affected fetal testis development. Ewes were treated by oral gavage from mating until euthanasia (d 134), producing three groups of fetuses with distinct adipose tissue PCB levels: high PCB 153/low PCB 118 (n = 13), high PCB 118/low PCB 153 (n = 14), and low PCB 153/low PCB 118 (n = 14). Fetal testes and blood samples were collected for investigation of testosterone, testis morphology, and testis proteome. The body weight of the offspring was lower in the high PCB compared to the low PCB group, but there were no significant differences in testis weight between groups when corrected for body weight. PCB exposure did not markedly affect circulating testosterone. There were no significant differences between groups in number of seminiferous tubules, Sertoli cell only tubules, and ratio between relative areas of seminiferous tubules and interstitium. Two-dimensional (2D) gel-based proteomics was used to screen for proteomic alterations in the high exposed groups relative to low PCB 153/low PCB 118 group. Twenty-six significantly altered spots were identified by liquid chromatography (LC)-mass spectroscopy (MS)/MS. Changes in protein regulation affected cellular processes as stress response, protein synthesis, and cytoskeleton regulation. The study demonstrates that in utero exposure to different environmental relevant PCB mixtures exerted subtle effects on developing fetal testis proteome but did not significantly disturb testis morphology and testosterone production.

Accumulation and effects of natural mixtures of persistent organic pollutants (POP) in Zebrafish after two generations of exposure.

Effects of exposure to environmentally realistic mixtures of persistent organic pollutants (POP) harvested from aquatic ecosystems in Norway were studied in an in vivo zebrafish model. POP were extracted from burbot (Lota lota) liver from two separate lakes, Lake Losna and Lake Mjøsa, and exposed to zebrafish through the diet in a two-generation study. Effects on survival, growth, sex ratio, and timing of puberty were investigated. In addition, the biomarkers 7-ethoxyresorufin O-deethylase (EROD) and vitellogenin (Vtg) were measured. The ratios of contaminant levels in extracts collected from Lake Mjøsa:Lake Losna were 6, 10, and 270 for polychlorinated biphenyls (PCB), dichlorodiphenyltrichloroethanes (DDT), and polybrominated diphenyl ethers (PBDE), respectively. The concentration range of POP measured in zebrafish was lower than in burbot originating from Lake Mjøsa, but comparable to concentrations previously reported in humans and wildlife. The results showed that exposure to environmentally realistic mixtures of POP exerted a negative effect on survival of fish in both generations. The marked drop in survival during 9-20 days post fertilization (dpf) suggested that this period may be a critical window for development. In both generations an earlier onset of puberty was observed and a higher proportion of males than females was noted in exposed fish compared to controls. Suprising effects of exposure were found on body weight. In the first generation (F(0)), body weight was significantly higher in both exposure groups compared to controls, while in the next generation (F(1)) the same exposures were associated with a decrease in body weight. Zebrafish exposed to relatively low quantities of POP showed a significant induction of biomarkers (EROD and Vtg), while fish exposed to higher exposure doses did not demonstrate induction.