Papers of the Month
By Sara Mishamandani Amolegbe
Insecticides affect circadian rhythm, increase type 2 diabetes risk
Chemicals commonly found in insecticides have been shown to disrupt insulin release and increase type 2 diabetes risk by interfering with the body’s circadian rhythm, according to a new study by NIEHS grantees. The study showed that certain carbamates, which are active ingredients in some insecticides, can bind to receptors normally reserved for melatonin, a hormone that plays a pivotal role in controlling circadian rhythm.
Melatonin regulates a wide array of processes, including blood sugar regulation. Abnormal melatonin activation can occur when other chemicals bind to the receptors that govern melatonin activity. Disrupting melatonin can inhibit other processes in the body, such as the release of insulin at night.
Using a computational approach, the researchers screened for chemicals that mimic the structure of melatonin and found that carbaryl and carbofuran carbamates could bind to specific melatonin receptors. Disruptions to these receptors, which normally activate melatonin to keep circadian rhythm in balance, were previously linked to elevated risk of developing type 2 diabetes.
The study points to a mechanism through which exposure to carbamate insecticides could affect insulin release and increase the risk of type 2 diabetes, among other potential effects on human health.
Popovska-Gorevski M, Dubocovich ML, Rajnarayanan RV. 2017. Carbamate insecticides target human melatonin receptors. Chem Res Toxicol 30(2):574–582.
New method strengthens study of effects from estrogen-like chemicals
NIEHS grantees developed a new method, using mouse mammary tissue, to test the direct effects of estrogen and estrogen-like substances on the developing mammary gland. Because the method completely isolates the fetal mammary glands from the mouse embryo, it removes the potential joint effects of maternal estrogen.
In previous studies, it was difficult to determine whether observed effects of bisphenol-A (BPA) were caused by estrogen-like activity or by other effects. This was because the estrogen-like chemicals interfered with maternal estrogens and could interrupt pregnancy. In the absence of maternal estrogen, researchers can isolate the effects of estrogen and estrogen-like chemical exposures on the development of fetal mammary tissue.
The researchers tested BPA, an estrogen-like chemical found in plastics, with the new method. They found that environmental levels of BPA significantly increased the growth of mammary gland tissue in the absence of natural estrogens that were previously linked to increased risk of breast cancer in adulthood. The findings show that BPA at low doses acts directly on the fetal mammary gland and leads to effects previously observed in other animal model studies.
Speroni L, Voutilainen M, Mikkola ML, Klager SA, Schaeberle CM, Sonnenschein C, Soto AM. 2017. New insights into fetal mammary gland morphogenesis: differential effects of natural and environmental estrogens. Sci Rep 7:40806.
Assessing computational models for traffic-related pollution
A new study by NIEHS grantees found that computer-based models of near-roadway air pollution agree in some, but not all, meteorological and building scenarios, and that models need to be selected that align with an area’s characteristics. The new study is one of the most comprehensive to date comparing near-road models of particulate air pollution on an hourly timescale.
Exposure to ultrafine particles, a type of air pollution emitted in motor vehicle exhaust, may contribute to increased risks of respiratory and cardiovascular disease. Potential exposures to ultrafine particles are measured as particle number concentrations (PNCs). Computational models have been used to measure PNCs near roadways.
The researchers evaluated four freely available models used in research and regulatory applications. They studied levels of near-roadway air pollution in a residential neighborhood, an urban center, and near highways in and around Boston. They found differences among models in areas with complex roadway geometries and wind patterns. They also found that the most important parameters affecting the predictions were the relationships between wind direction and particle source and building locations. They also discovered that the models underpredicted, by a factor of three, the PNCs in areas less than 50 meters from the edge of the highway.
The team identified the model approach that most accurately predicted PNCs based on the type of study area. They included hybrid approaches that used multiple models. According to the authors, their methods and results are useful to hourly models of PNCs in similar urban areas near highways.
Patton AP, Milando C, Durant JL, Kumar P. 2017. Assessing the suitability of multiple dispersion and land use regression models for urban traffic-related ultrafine particles. Environ Sci Technol 51(1):384–392.
Identifying sensitive windows of prenatal exposure to air pollution
NIEHS grantees found that increased prenatal exposure to particulate matter less than 2.5 micrometers (PM2.5) during a specific portion of the third trimester may increase oxidative stress and susceptibility to health effects mediated by white blood cells, such as infections and immune response to allergens. During this window in late pregnancy, increased exposure to PM2.5 air pollution was associated with lower mitochondrial DNA content in cord blood, a marker of oxidative stress. Oxidative stress is an imbalance in the production of free radicals and the body’s ability to counteract their harmful effects.
The study involved participants in the NIH-funded Programming Research in Obesity, Growth, Environment, and Social Stressors cohort in Mexico City The researchers measured the mitochondrial DNA content of white blood cells in umbilical cord blood collected from mothers at delivery. They also estimated daily exposure to PM2.5 during pregnancy using a satellite method that estimates particulate levels across Mexico City.
The researchers compared the exposure levels during pregnancy to the mitochondrial DNA content in white blood cells at birth. They found that babies were more sensitive to mitochondrial DNA changes when they had higher exposures to PM2.5 during gestation weeks 35 to 40. They also found that PM2.5 was more strongly associated with differences in mitochondrial DNA content in boys compared with girls.
Rosa MJ, Just AC, Guerra MS, Kloog I, Hsu HL, Brennan KJ, Garcia AM, Coull B, Wright RJ, Tellez Rojo MM, Baccarelli AA, Wright RO. 2017. Identifying sensitive windows for prenatal particulate air pollution exposure and mitochondrial DNA content in cord blood. Environ Int 98:198–203.