Papers of the Month
By Megan Avakian
Nanoparticles inhaled during pregnancy can cross the rodent placenta, exposing fetus
Inhaled nanoparticles (NPs) can travel from a pregnant mother’s lungs and cross the placenta to potentially expose the fetus, according to an NIEHS-funded study in rats. NPs are used in many commercial products, including sunscreens, cosmetics, and pharmaceuticals.
Researchers exposed rats to air with titanium dioxide nanoparticles throughout pregnancy. Then they measured concentrations of titanium in maternal, placental, and fetal tissues. Using imaging techniques, they also visualized NP accumulation in placental cells.
Titanium was detected in various organs and tissues of exposed mothers, including the liver, kidney, uterus, placenta, spleen, heart, blood, pancreas, and ovaries. Fetuses of exposed rats had significantly higher titanium in the umbilical cord and heart compared with controls. In exposed rats, there was on average 40.6 parts per billion (ppb) titanium measured on the maternal side of the placenta and 36.3 ppb on the fetal side, indicating that titanium accumulated similarly in both zones. NP clusters were detected within the nucleus, rough endoplasmic reticulum, and vesicles of placental cells.
According to the authors, results suggest that inhaled NPs can be distributed throughout the body to other tissues and organs, including the placenta, in both mothers and their developing offspring. Given the many critical roles the placenta plays during pregnancy to protect fetal development, additional research is needed to better understand how NP exposure may impact placental function.
Citation: D'Errico JN, Doherty C, Reyes George JJ, Buckley B, Stapleton PA. 2022. Maternal, placental, and fetal distribution of titanium after repeated titanium dioxide nanoparticle inhalation through pregnancy. Placenta 121:99–108.
Cytokine aids mouse lung repair following exposure to agricultural dust
NIEHS-funded researchers identified a novel role for the cytokine IL-22 in lung repair following exposure in mice to agricultural dust. Many agricultural workers experience inflammatory lung diseases, such as asthma. Although IL-22 is upregulated in such lung diseases, it has shown conflicting involvement in both lung repair and inflammation.
The study included 6-8–week-old mice missing the IL-22 gene, called knockout mice, and normal mice. The researchers exposed mice to organic dust extracts from hog confinement facilities for three weeks. Then they assessed changes in gene and protein expression and morphological changes in the lung.
In normal mice, IL-22 was expressed in lung epithelium and in lung cells that promote tissue repair. IL-22 expression was accompanied by increases in an IL-22 receptor within the lung epithelium. Compared with normal mice, knockout mice had an enhanced response to dust exposure as evidenced by a higher number of immune cells moving into the lung and greater tissue damage.
The researchers also assessed expression of IL-22 in a human white blood cell line, finding that IL-22 increased following dust exposure. IL-22 was localized in the Golgi and released following exposure. This suggests that cells package IL-22 in the Golgi and only release it in the presence of an inflammatory insult.
These study results support a protective role for IL-22 following agricultural dust exposure. Findings may inform development of therapeutics that could benefit patients with environmentally induced lung disease, said the authors.
Citation: Ulu A, Sveiven S, Bilg A, Velazquez JV, Diaz M, Mukherjee M, Yuil-Valdes AG, Kota S, Burr A, Najera A, Nordgren TM. 2022. IL-22 regulates inflammatory responses to agricultural dust-induced airway inflammation. Toxicol Appl Pharmacol 446:116044.
Filters alter bacterial community in water, affecting fish gut microbiome and behavior
Water filters altered the bacterial community in drinking water in ways that influenced the gut microbiome and behavior in larval zebrafish, found NIEHS-funded researchers. Water filters remove unwanted chemicals from drinking water. However, they also can support bacterial growth and significantly change the bacterial composition of drinking water over time.
The study included larval and adult zebrafish exposed to tap water or water filtered using activated carbon block point-of-use filters. The researchers assessed zebrafish behavior using a locomotor activity test and characterized the gut microbiome. They examined effects at early and late stages of filter operation.
The gut microbiome of larvae exposed to filtered water was significantly different from that of tap-exposed larvae. Larvae exposed to filtered water had different gut microbiome composition between early and late filter stages, whereas the gut microbiome remained relatively consistent over time in tap-exposed larvae. The team attributed these differences to bacterial changes in the water after filtration. Adult zebrafish gut microbiomes were not affected by either water type or filter stage.
Larvae exposed to filtered water and late-stage tap water exhibited hyperactive behavior. The relative abundance of bacteria important in gut-brain communication was significantly lower in the hyperactive larvae compared with those that behaved normally.
According to the team, drinking water from activated carbon block filters, particularly early in life, may have important health implications for humans.
Citation: Wu CC, Connell M, Zarb A, Akemann C, Morgan S, McElmurry SP, Love NG, Baker TR. 2022. Point-of-use carbon-block drinking water filters change gut microbiome of larval zebrafish. Environ Microbiol Rep; doi:10.1111/1758-2229.13077 [Online 6 May 2022].
Prenatal bisphenol exposure may alter cardiovascular development, increase disease risk
Prenatal exposure to bisphenol chemicals influenced child cardiovascular development, found NIEHS-funded researchers. This study is the first to assess the association of maternal bisphenol and phthalate exposure on arterial development in children. These chemicals can cross the placenta to expose the fetus, which may impair arterial and heart development and predispose individuals to cardiovascular disease in later life.
This population-based study included 935 pregnant mothers and their children from the Netherlands. The researchers measured maternal urinary phthalate and bisphenol concentrations at each trimester. They assessed two measures of arterial damage — increased carotid intima-media thickness and decreased distensibility — in the children at age 10 years using ultrasound. These measures are associated with cardiovascular disease risk factors in children, such as obesity and high blood pressure.
Higher average and third-trimester maternal concentrations of total bisphenol, especially bisphenol A (BPA), were associated with a lower carotid intima-media thickness. Although increased carotid intima-media thickness is generally associated with higher cardiovascular disease risk, the researchers hypothesized that a thinner carotid intima-media may represent underdevelopment of the vascular system. Maternal phthalate concentrations were not associated with child carotid intima-media thickness. Neither maternal bisphenol nor phthalate concentrations were associated with child carotid distensibility.
The authors called for additional studies to replicate this association and to identify potential underlying mechanisms.
Citation: Blaauwendraad SM, Gaillard R, Santos S, Sol CM, Kannan K, Trasande L, Jaddoe VWV. 2022. Maternal phthalate and bisphenol urine concentrations during pregnancy and early markers of arterial health in children. Environ Health Perspect 130(4):47007.