Gestational and lactational exposure to the polychlorinated biphenyl mixture Aroclor 1254 modulates retinoid homeostasis in rat offspring
- DOI
- Language of the publication
- English
- Date
- 2014-06-01
- Type
- Article
- Author(s)
- Esteban, Javier
- Elabbas, Lubna E.
- Borg, Daniel
- Herlin, Maria
- Åkesson, Agneta
- Barber, Xavier
- Hamscher, Gerd
- Nau, Heinz
- Bowers, Wayne J.
- Nakai, Jamie S.
- Viluksela, Matti
- Håkansson, Helen
- Publisher
- Elsevier
Abstract
Polychlorinated biphenyls (PCBs) induce a broad spectrum of biochemical and toxic effects in mammals including alterations of the vital retinoid (vitamin A) system. The aim of this study was to characterize alterations of tissue retinoid levels in rat offspring and their dams following gestational and lactational exposure to the PCB mixture Aroclor 1254 (A1254) and to assess the interrelationship of these changes with other established sensitive biochemical and toxicological endpoints. Sprague-Dawley rat dams were exposed orally to 0 or 15 mg/kg body weight/day of A1254 from gestational day 1 to postnatal day (PND) 23. Livers, kidneys and serum were collected from the offspring on PNDs 35, 77 and 350. Tissue and serum retinoid levels, hepatic cytochrome P450 (CYP) enzymes and serum thyroid hormones were analyzed. A multivariate regression between A1254 treatment, hepatic retinoid levels, hepatic CYP enzymes activities, thyroid hormone levels and body/liver weights was performed using an orthogonal partial least-squares (PLS) analysis. The contribution of dioxin-like (DL) components of A1254 to the observed effects was also estimated using the toxic equivalency (TEQ) concept. In both male and female offspring short-term alterations in tissue retinoid levels occurred at PND35, i.e. decreased levels of hepatic retinol and retinoic acid (RA) metabolite 9-cis-4-oxo-13,14-dihydro-RA with concurrent increases in hepatic and renal all-trans-RA levels. Long-term changes consisted of decreased hepatic retinyl palmitate and increased renal retinol levels that were apparent until PND350. Retinoid system alterations were associated with altered CYP enzyme activities and serum thyroid hormone levels as well as body and liver weights in both offspring and dams. The estimated DL activity was within an order of magnitude of the theoretical TEQ for different endpoints, indicating significant involvement of DL congeners in the observed effects. This study shows that tissue retinoid levels are affected both short- and long-term by developmental A1254 exposure and are associated with alterations of other established endpoints of toxicological concern.
Plain language summary
Health Canada conducts research on the effects of chemicals in support of its mandate to assess the health risks to Canadians of various chemicals, including in potentially more vulnerable northern populations. Arctic inhabitants are often exposed to chemical pollutants because they consume large amounts of fish and marine mammals in their traditional diets. These pollutants are difficult to break down and eliminate and have the potential to cause adverse health effects. Fetuses and newborns are especially susceptible to the health effects of these chemicals. Because humans continue to be exposed to PCBs, this study used a commercial mixture of PCBs (Aroclor 1254) to test the effects of this mixture by administering it to pregnant rats and observing the effect on the offspring who received it during fetal development and in the mother's milk. Because vitamin A (retinoids) is essential for development, the effects of the PCB mixture on vitamin A levels in the liver, kidney and blood were examined in the offspring as young, mature and old animals. Exposure to the chemical mixture altered liver vitamin A retinoid levels at all ages, but the largest effects were in the youngest animals. The effect of the PCB mixture on vitamin A was related to the effect of the chemicals on liver function and thyroid hormone levels. This study suggests that altered vitamin A status may be an important effect of exposure to chemical pollutants. These results will be considered in the context of better identifying the human health effects of exposure to PCBs and other chemical pollutants in vulnerable populations, including in the north.
Subject
- Health,
- Health and safety