Fetal adrenal development: Comparing effects of combined exposures to PCB 118 and PCB 153 in a sheep model

Abstract

This study investigated the effects of exposure to the ubiquitous contaminants polychlorinated biphenyls (PCBs) on the fetal adrenal cortex and on plasma cortisol using the domestic sheep (Ovis aries) as a model. Pregnant ewes were intendedly subjected to oral treatment with PCB 153 (98 μg/kg bw/day), PCB 118 (49 μg/kg bw/day) or the vehicle corn oil from mating until euthanasia on gestation day 134 (±0.25 SE). However, because of accidental cross-contamination occurring twice causing a mixed exposure scenario in all three groups, the focus of this paper is to compare three distinct groups of fetuses with different adipose tissue PCB levels (PCB 153high, PCB 118high and low, combined groups) rather than comparing animals exposed to single PCB congeners to those of a control group. When comparing endocrine and anatomical parameters from fetuses in the PCB 153high (n = 13) or PCB 118high (n = 14) groups with the low, combined group (n = 14), there was a significant decrease in fetal body weight (P < 0.05), plasma cortisol concentration (P < 0.001) and adrenal cortex thickness (P < 0.001). Furthermore, adrenal weight was decreased and plasma ACTH was increased only in the PCB 118high group. Expression of several genes encoding enzymes and receptors related to steroid hormone synthesis was also affected and mostly down-regulated in fetuses with high PCB tissue levels. In conclusion, we suggest that mono-and di-ortho PCBs were able to interfere with growth, adrenal development and cortisol production in the fetal sheep model. © 2011 Wiley Periodicals, Inc. Environ Toxicol, 2013.

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

“…The present study is a part of a research program including female and male offspring, and there are several publications that focus on aspects other than the testes. Zimmer et al (2011) found that plasma cortisol concentration and adrenal cortex thickness were significantly reduced. Further, adrenal weight was decreased and plasma ACTH was increased only in the H-118/L-153 group.…”

“…The results from the PCB analyses have been published by Zimmer et al (2011) ( Table 1). The mixture exposures led to three distinct exposure scenarios, including a high PCB 153, low PCB 118 exposed group (H-153/L-118), a high PCB 118, low PCB 153 exposed group (H-118/L-153), and a group with considerably lower tissue concentrations of both congeners (L-153/L-118), as determined by PCB concentrations in adipose tissue.…”

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.…”

Lipopolysaccharide potentiates polychlorinated biphenyl-induced disruption of the blood–brain barrier via TLR4/IRF-3 signaling

“…Treatment of mice with Aroclor 1254 (a commercial PCB mixture) disrupted spermatogenesis, as evidenced by decreased sperm count, testicular dysgenesis, and lowered estradiol levels (Cai et al 2011). Oral treatment with selected PCB congeners also affected growth, adrenal development, and cortisol production in a fetal sheep model (Zimmer et al 2011). Developmental oral exposure to PCB52 or PCB180 induced alterations of the brainstem auditory evoked potentials (Lilienthal et al 2011).…”