Papers of the Month
By Adeline Lopez
Women with gestational diabetes may transfer more PFAS to fetus
Women with gestational diabetes may transfer more per- and polyfluoroalkyl substances (PFAS) to their fetuses than women without gestational diabetes, according to an NIEHS-funded study. PFAS are synthetic chemicals found in a wide variety of consumer products that have been linked with a variety of health problems, including cancer, and impacts on hormone levels, the immune system, and development.
The researchers analyzed blood and umbilical cord samples from 151 mother-newborn pairs in the Faroe Islands to determine the amount of 17 PFAS compounds transferred from mom to baby. They found that women with higher PFAS concentrations in their blood were more likely to have babies with higher PFAS concentrations in cord blood. They also identified specific characteristics of different PFAS compounds that were important predictors of maternal transfer. They reported that gestational diabetes was also a strong predictor of transfer, with significantly higher transfer of PFAS among mothers with gestational diabetes than those without.
The team reported high maternal transfer for certain PFAS compounds with a longer chain of linked carbon atoms, which may raise health concerns, because the toxicity of PFAS tends to increase with increasing carbon chain length. According to the authors, their results point to important factors in maternal transfer of PFAS that can inform how scientists study human exposure and potential health risks.
Citation: Eryasa B, Grandjean P, Nielsen F, Valvi D, Zmirou-Navier D, Sunderland E, Weihe P, Oulhote Y. 2019. Physico-chemical properties and gestational diabetes predict transplacental transfer and partitioning of perfluoroalkyl substances. Environ Int 130:104874.
Mitochondrial chain reaction damages telomeres
NIEHS grantees demonstrated for the first time that damaged mitochondria, the powerhouses of a cell, can trigger a harmful chain reaction that results in telomere damage. Telomeres protect the ends of chromosomes and play an important role in cell division and aging.
The team developed and used a new targeted approach to study mitochondrial damage that generates a short-lived, highly reactive singlet oxygen, a type of harmful reactive oxygen species (ROS) inside the mitochondria when exposed to light. ROS are chemically reactive molecules involved in inflammation, aging, and cancer. The researchers observed that exposure to this singlet oxygen resulted in decreased mitochondrial function and mitochondrial fragmentation, an important early event that can lead to cell death. They also found that the singlet oxygen produced a persistent secondary wave of ROS within the mitochondria.
By following the movement of ROS, they reported direct evidence that mitochondrial ROS can travel to the cell nucleus and damage telomeres, causing fragility and DNA double strand breaks in this important region. In a similar experiment in cells without mitochondrial DNA, they reported no ROS accumulation and no telomere damage.
According to the authors, their findings may represent a key event that produces favorable conditions for cancer cells by creating a feedback loop that amplifies cell damage, particularly DNA damage at telomeres. They suggest this chain of events may underlie the molecular processes involved in cancer and other diseases.
Citation: Qian W, Kumar N, Roginskaya V, Fouquerel E, Opresko PL, Shiva S, Watkins SC, Kolodieznyi D, Bruchez MP, Houten BV. 2019. Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction. Proc Natl Acad Sci U S A 116(37):18435−18444. (Story)
Changes in brain activity linked to prenatal pesticide exposure
Teens who had higher prenatal exposure to organophosphate pesticides had altered brain activity while performing certain tasks, according to a new NIEHS-funded study. Although prenatal exposure to these pesticides has been linked to poor cognition and behavior problems in children, this study is the first to demonstrate specific changes in the brain that may help explain why.
The team used an imaging technique called functional near-infrared spectroscopy (fNIRS) to visualize blood flow and activity in different brain regions. They monitored the brains of 95 teens aged 15 to 17 years who performed tasks related to executive function, attention, social cognition, and language comprehension. Prenatal exposure to pesticides was estimated for each of the teens based on their mother’s residential proximity to pesticide use during pregnancy. Compared with those with lower estimated exposure, teens with higher estimated prenatal pesticide exposure were found to have less blood flow to the frontal cortex while performing tasks related to cognitive flexibility and visual memory but had higher blood flow to the parietal and temporal lobes during tests recalling words.
According to the authors, decreased activation during the more complex tasks may point to altered overall neural response, whereas increased activation may indicate higher cognitive demand to complete simpler tasks. They suggest that fNIRS is an inexpensive and practical alternative to neuroimaging for understanding the impact of environmental exposures on brain function.
Citation: Sagiv SK, Bruno JL, Baker JM, Palzes V, Kogut K, Rauch S, Gunier R, Mora AM, Reiss AL, Eskenazi B. 2019. Prenatal exposure to organophosphate pesticides and functional neuroimaging in adolescents living in proximity to pesticide application. Proc Natl Acad Sci U S A 116(37):18347−18356.
Cataloguing genetic diversity of the human microbiome
According to a new NIEHS-funded study, the human body contains microbes with staggering genetic variation, much of which is unique to a single individual. The study, one of the largest of its kind, is the first to look at the DNA of bacteria that reside in both the mouth and the gut. Most previous research has focused on identifying the types of bacteria, rather than their full genome, providing only partial clues to how the microbiome is involved in disease and health.
The team aggregated publicly available microbiome data from nearly 4,000 samples from the human mouth and gut and used computational approaches to identify unique genes. Their analysis uncovered a massive universe of more than 45 million unique bacterial genes. Many of these were found in only one sample, pointing to vast genetic variation within bacterial strains. They reported that these unique genes could be profiled to act as microbial fingerprints, which may provide important information about past exposures.
Together, this information was used to build a publicly available microbiome gene catalog. According to the authors, cataloguing the array of microbial genes could help explain observed differences in human diseases in which the microbiome is known to play a role. The catalogue could also shed light on the interaction between genes and the environment that leads to health or disease.
Citation: Tierney BT, Yang Z, Luber JM, Beaudin M, Wibowo MC, Baek C, Mehlenbacher E, Patel CJ, Kostic AD. 2019. The landscape of genetic content in the gut and oral human microbiome. Cell Host Microbe 26(2):283−295.e8.
(Adeline Lopez is a science writer for MDB Inc., a contractor for the NIEHS Superfund Research Program.)