In Utero Exposure to Environmentally Relevant Concentrations of PCB 153 and PCB 118 Disrupts Fetal Testis Development in Sheep

Abstract

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.

Cross-species toxicogenomic analyses and phenotypic anchoring in response to groundwater low-level pollution

“…These findings agreed with the suggestion that functional pathways could be better and reliable markers than single genes. This observation is consistent with the documented effect of several water pollutants (metals, plasticizers and others) on hormonal axes linked to reproductive health outcomes [ 60 – 64 ], as seen also in our experimental settings (manuscript in preparation). Here, toxicogenomics showed its predictive strength in identifying biomarkers, steroid hormones, that can be easily detected in blood, suitable for monitoring the impact of anthropogenic activities on human and identifying risks for human populations even if not indicative of specific pollutants.…”

Risk for animal and human health related to the presence of dioxins and dioxin‐like PCBs in feed and food

“…Eight papers on potential effects of PCDD/Fs and DL‐PCBs in sheep were identified (Annex A.11.1, Table 88 therein). Three of these concerned the same study with sheep treated with PCB‐118 (Gutleb et al., ; Zimmer et al., ; Krogenaes et al., ). There was apparently a cross‐contamination with PCB‐153 and standards were not checked for the presence of more potent DL‐PCBs and PCDD/Fs.…”

Chlorinated biphenyls effect on estrogen-related receptor expression, steroid secretion, mitochondria ultrastructure but not on mitochondrial membrane potential in Leydig cells

“…Data obtained from laboratory animals emphasized the pleiotropic nature of PCBs effects and the susceptibility of both developing and adult reproductive systems. In sheep exposed in utero , PCBs exerted subtle effects on fetal testis proteome but did not significantly disturb testis morphology and testosterone synthesis (Krogenæs et al 2014 ). Neonatal PCBs treatment increased testis weight and daily sperm production in adult rats, through induction of hypothyroidism, which led to an increase in Sertoli cell number (Cooke et al 1996 ).…”