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Environmental Factor, December 2012

Extramural papers of the month

By Nancy Lamontagne

Srp logo : Read the current Superfund Research Program "Research Brief". New issues are published on the first Wednesday of each month.

BPA exposure linked to thyroid level changes for pregnant women and newborns

A new study from NIEHS grantees links levels of urine bisphenol A (BPA) in pregnant women to changes in thyroid hormone levels for the women and their newborn boys. Thyroid hormone is necessary for healthy brain development, and the new findings add to growing health concerns about BPA.

The researchers studied 476 women participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal study, which is examining environmental exposures and health among pregnant women and children. They measured BPA concentration in urine samples collected from the women during the first and second half of pregnancy, as well as free and total levels of thyroxine hormone and thyroid-stimulating hormone. The investigators also measured thyroid-stimulating hormone in the newborns.

The average maternal BPA concentration was associated with reduced thyroid-stimulating hormone in boys, but not in girls. Among boys, the link was stronger for BPA measurements taken in the third trimester of pregnancy and decreased with time between BPA and thyroid hormone measurements.

The researchers say their results suggest that maternal BPA either has a transient effect on thyroid-stimulating hormone in the newborn, or that there is a developmental window of susceptibility. Further studies are needed to better understand the relationship.

CitationChevrier J, Gunier RB, Bradman A, Holland NT, Calafat AM, Eskenazi B, Harley KG. 2012. Maternal Urinary Bisphenol A During Pregnancy and Maternal and Neonatal Thyroid Function in the CHAMACOS Study. Environ Health Perspect; doi:10.1289/ehp.1205092 [Online 4 Oct. 2012].

PCBs impair glucose homeostasis in mice

There is growing evidence that PCB exposure is linked to increased risk for type 2 diabetes. A new mouse study from NIEHS grantees provides insight into how coplanar PCBs affect gene expression and accumulate in body fat in a way that leads to problems with regulating glucose.

Because studies suggest that PCB exposure levels are associated with diabetes even in lean individuals, the researchers initiated studies in mice fed a low-fat diet. They also conducted studies in mice made obese from consumption of a high-fat diet, and in a group of obese mice made to lose weight by switching to the low-fat diet. Some mice from all the diet groups received PCB-77, and others served as controls.

The researchers measured glucose and insulin tolerance, as well as levels of tumor necrosis factor alpha (TNF-alpha) in adipose (body fat), liver, and muscle tissue. TNF-alpha is known to contribute to insulin resistance. In vivo and in vitro experiments revealed that interfering with aryl hydrocarbon receptors (AhR) stopped the effects of PCB-77, indicating that an AhR-dependent mechanism was involved. The researchers concluded that adipose-specific elevations in TNF-alpha expression may contribute to impaired glucose homeostasis, or stability.

CitationBaker NA, Karounos M, English V, Fang J, Wei Y, Stromberg A, Sunkara M, Morris AJ, Swanson HI, Cassis LA. 2012. Coplanar Polychlorinated Biphenyls Impair Glucose Homeostasis in Lean C57BL/6 Mice and Mitigate Beneficial Effects of Weight Loss on Glucose Homeostasis in Obese Mice. Environ Health Perspect; doi:10.1289/ehp.1205421 [Online 24 October 2012].

Childhood air pollution exposure and adult heart health

Childhood exposure to ozone can increase risk for higher carotid artery intima-media thickness (CIMT) in healthy young adults, according to a study from NIEHS grantees. Increased CIMT thickness marks plaque buildup in artery walls, which increases risk for later cardiovascular disease.

To study the effects of childhood exposure to air pollution, the researchers estimated childhood and lifetime exposures to particulate matter (PM), nitrogen dioxide, and ozone for 861 University of Southern California college students, using their home addresses and the U.S. Environmental Protection Agency’s Air Quality System database. The investigators also collected health and sociodemographic information, and analyzed lipids and biomarkers in blood samples. 

As a whole, study participants had an average CIMT of 603 micrometers. However, individuals exposed to ozone from birth to age 5, had an average CIMT 7.8 micrometers higher as young adults, and those exposed from ages 6 to 12 had an average 10.1 micrometers higher. Lifetime exposure to ozone showed similar, but not significant associations. The researchers say their findings point to the importance of regulating air pollutants and limiting childhood exposures to ozone.

CitationBreton CV, Wang X, Mack WJ, Berhane K, Lopez M, Islam TS, Feng M, Lurmann F, McConnell R, Hodis HN, Kunzli N, Avol E. 2012. Childhood Air Pollutant Exposure and Carotid Artery Intima-media Thickness in Young Adults. Circulation 126(13):1614-1620.

Dioxin induces disease and reproductive problems in later generations

NIEHS grantees report that dioxin, specifically TCDD, administered to pregnant rats, created epigenetic changes that led to a variety of reproductive problems and adult-onset disease in subsequent generations.

Pregnant rats received TCDD during fetal days eight to 14. The first generation of rats showed increased incidences of total disease and multiple diseases, including prostate and polycystic ovarian disease, and fewer ovarian follicles. Third generation males had kidney disease, and females had pubertal abnormalities, ovarian primordial follicle loss, and polycystic ovary disease.

Investigators also analyzed epigenetic changes in the third generation sperm, finding 50 differentially DNA methylated regions in gene promoters. These regions offer potential epigenetic biomarkers for transgenerational disease and ancestral environmental exposures.

CitationManikkam M, Tracey R, Guerrero-Bosagna C, Skinner MK. 2012. Dioxin (TCDD) Induces Epigenetic Transgenerational Inheritance of Adult Onset Disease and Sperm Epimutations. PLoS One 7(9):e46249.

(Nancy Lamontagne is a science writer with MDB, Inc., a contractor for the NIEHS Division of Extramural Research and Training, Superfund Research Program, and Worker Education and Training Program.)

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