Project #2: Postnatal Complications of Perinatal Polychlorinated Biphenyl Exposure
It is well established that a variety of toxic insults during pregnancy, e.g., cigarette smoking, drug use, and alcohol abuse, can negatively impact maternal and fetal health and can program offspring for increased risk of later life diseases. Fortunately, pregnant women can choose whether to modify these risky behaviors. Unfortunately, there is no choice when it comes to exposure to environmental contaminants; however, exercise or other interventions could provide a novel means to protect exposed parents and children from the detrimental effects.
Polychlorinated biphenyls (PCBs), one of a number of chlorinated organic pollutants, are highly lipid-soluble toxins that are characterized by relative chemical stability and prevalence in the environment. These traits are responsible for their widely recognized role as a source of serious environmental public health risks. PCBs have been shown to cross the placenta and enter breast milk, and recent data suggests that prenatal organochlorine levels contribute to gender-specific obesity development in children. In a mouse model, observations from our laboratory revealed that offspring exposed perinatally to PCBs had significantly worse fat and lean mass profiles compared to offspring born to vehicle-treated dams. Further, mature offspring born to PCB-exposed dams had impaired glucose tolerance compared to offspring from vehicle-treated dams. Separately, we have shown that maternal exercise prior to and during healthy pregnancy and nursing can enhance long-term glucose homeostasis in offspring. The goal of our ongoing research is to elucidate the potential long-term health complications and mechanisms of PCB toxicity during the critical periods of in utero and early postnatal life and to explore maternal exercise as a transgenerational intervention.
UK-SRC studies are providing new etiological evidence supporting current observations that perinatal exposures to environmental PCBs are important contributors to the epidemic of diabetes in the United States. This work will also contribute innovative new insights to understanding the role of exercise in mitigating the environmental health impacts of PCB exposure by highlighting pregnancy as a sensitive period when environmental pollutants could have significant and long-lasting effects on offspring metabolism and when interventions could prove effective in ameliorating the detrimental health outcomes. Anticipated results are particularly significant in that they highlight early developmental stages, i.e., fetal and neonatal, as potential periods of particular vulnerability to lasting effects of toxic environmental insult from PCB contamination.
- To establish the importance of the timing of perinatal PCB exposure that precipitates impaired glucose tolerance in offspring.
- To elucidate the mechanism of impaired insulin sensitivity in offspring born to PCB-exposed dams.
- To test if voluntary maternal exercise can be used as an intervention to protect adult offspring from the long-term effects of perinatal PCB exposure.
- Rashid, C., Carter, L.G., Hennig, B., and Pearson, K.J. Perinatal polychlorinated biphenyl 126 exposure alters offspring body composition. (2013) Journal of Pediatric Biochemistry, 3(1):47-53. PMCID: PMC3670830
- Baker, N.A., English, V., Sunkara, M., Morris, A.J., Pearson, K.J., and Cassis, L.A., Resveratrol protects against polychlorinated biphenyl-mediated impairment of glucose homeostasis in adipocytes. (2013) Journal of Nutritional Biochemistry, 24(12):2168-74. PMCID: PMC4066417
- Carter, L.G., Ngo Tenlep, S.Y., Woollett, L.A., and Pearson, K.J. Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet. (2015) Journal of Diabetes and Metabolism, 6(12): pii: 634. PMCID: PMC4782803
- Swanson, H.I. Drug Metabolism by the Host and Gut Microbiota: A Partnership or Rivalry? (2015) Drug Metabolism and Disposition, 43:1499-1504. PMCID: PMC4576677
- Platt, K.M., Charnigo, R.J., Shertzer, H.G., and Pearson, K.J. Branched-Chain Amino Acid Supplementation in Combination with Voluntary Running Improves Body Composition in Female C57BL/6 Mice. (2016) Journal of Dietary Supplements, 13(5):473-86. PMCID: PMC4788571
- Preston, J.D., Reynolds, L.J., and Pearson, K.J. Developmental Origins of Health Span and Life Span: A Mini Review. (2018) Gerontology, 64:237-245. PMID: 29324453
Project #2 PI Dr. Kevin Pearson: Hear Why Kevin Loves Medical Research
UK Superfund Postdoctoral Trainee Leryn Reynolds, PhD