Papers of the Month
By Megan Avakian
Air pollution may speed up bone loss in postmenopausal women
Elevated exposure to air pollution was associated with reduced bone density among postmenopausal women, NIEHS-funded scientists found. This research is the first to assess the effects of air pollution mixtures on bone health in women who have already undergone menopause.
The study included data from more than 9,000 participants enrolled in the Women’s Health Initiative, an ethnically diverse cohort of postmenopausal women in the U.S. The researchers linked participants’ home addresses with publicly available air pollution data to estimate average daily exposure to particulate matter, nitrogen oxide, nitrogen dioxide, and sulfur dioxide. Over a six-year period, they measured bone mineral density (BMD) at the total hip, hip joint, lower spine, and whole body. The researchers examined the relationship between BMD and exposure to individual air pollutants as well as a mixture of all four pollutants.
For each of the four pollutants, the researchers found that women with elevated exposures had lower BMD at the total hip, hip joint, lower spine, and whole body. The lower spine was the site most susceptible to bone loss. Damage from nitrogen oxides on lower spine BMD was nearly twice that seen with normal aging. Mixtures analysis revealed that nitrogen oxides contributed the most to bone loss, even at levels below current national air quality standards.
According to the authors, results confirmed that poor air quality may be a risk factor for bone loss and suggest that policies to reduce air pollution, especially nitrogen oxides, can help protect bone health among aging women.
Citation: Prada D, Crandall CJ, Kupsco A, Kioumourtzoglou MA, Stewart JD, Liao D, Yanosky JD, Ramirez A, Wactawski-Wende J, Shen Y, Miller G, Ionita-Laza I, Whitsel EA, Baccarelli AA. 2023. Air pollution and decreased bone mineral density among Women's Health Initiative participants. EClinicalMedicine 57:101864.
Uncovering how algal toxin may initiate nervous system dysfunction
NIEHS-funded researchers identified how early-life exposure to domoic acid (DomA), a neurotoxin produced by some types of algae, may disrupt neurodevelopment. Humans are exposed to DomA through contaminated seafood, and high levels of exposure can cause memory loss, seizures, and even death. However, little is known about how early-life exposure to the toxin affects nervous system development and function.
The study focused on how DomA disrupts myelination, the process by which a fatty substance called myelin wraps around neurons. Specialized cells called oligodendrocytes produce myelin, which encases the long, threadlike part of a neuron — called the axon — and helps brain signals travel through the body.
The researchers wanted to identify the cells first targeted by DomA before myelination occurs. They exposed two-day-old zebrafish larvae to DomA, then used microscopy techniques to assess the effects of DomA on neuron number and myelin structure.
DomA exposure led to the loss of axons on hindbrain neurons involved in movement. The finding suggested that myelin may form around other parts of neurons where it does not usually occur, according to the authors. This abnormal myelination may happen when fewer axons are available relative to the number of oligodendrocytes present.
To test that hypothesis, the researchers treated DomA-exposed larvae with a chemical that reduces oligodendrocyte number. They found that when oligodendrocytes decreased, so did the number of abnormally myelinated features.
Together, these findings suggest that DomA targets specific neurons to alter the cellular environment in ways that lead to defective myelination, providing clues into how the toxin alters neurodevelopment.
Citation: Panlilio JM, Hammar KM, Aluru N, Hahn ME. 2023. Developmental exposure to domoic acid targets reticulospinal neurons and leads to aberrant myelination in the spinal cord. Sci Rep 13(1):2587.
Nanoplastics cross through placenta from mother to fetus in vivo
Tiny plastic fragments ingested during pregnancy can cross the placenta to expose the unborn fetus, according to an NIEHS-funded study using rats. These miniscule pieces, collectively called micro- and nanoplastics (MNPs), appear throughout the environment and food web. Humans inadvertently consume MNPs in contaminated water or food, and research suggests that MNP exposure during pregnancy adversely affects birth outcomes and fetal health.
To move from mother to fetus, ingested MNPs must first breach the wall of the intestine to access the mother’s circulatory system and subsequently cross the placenta to reach the fetal blood stream and tissues. The researchers tracked this movement by exposing pregnant rats to nanoplastic spheres through a feeding tube. A day later, they used specialized imaging techniques to identify and visualize the nanoplastics that had accumulated in placental and fetal tissues.
They discovered abundant nanoplastics within placental and fetal tissues. They observed nanoplastics in all fetal tissues examined, including the liver, kidney, heart, lung, and brain, where they amassed in large clusters. This clustering suggests that nanoplastics may have been taken up by fetal blood cells, said the authors.
The findings demonstrate that ingested MNPs can traverse the intestinal and placental barriers to reach fetal circulation and tissues, according to the authors. They called for additional research to examine how particle size, shape, and other properties may affect MNP movement throughout the body and to understand potential health implications of fetal MNP exposure.
Citation: Cary CM, DeLoid GM, Yang Z, Bitounis D, Polunas M, Goedken MJ, Buckley B, Cheatham B, Stapleton PA, Demokritou P. 2023. I ngested polystyrene nanospheres translocate to placenta and fetal tissues in pregnant rats: potential health implications. Nanomaterials (Basel) 13(4):720.
DNA methylation may explain impact of indoor air pollution on neurodevelopment
A biological process called DNA methylation may be the key to understanding how prenatal exposure to indoor air pollution alters neurodevelopment, NIEHS-funded researchers found. During methylation, a compound called a methyl group binds to DNA, turning genes on or off. Exposure to air pollution and other environmental factors can alter DNA methylation patterns to adversely affect health.
Although research links outdoor air pollution exposure and nervous system dysfunction, the scientists wanted to better understand the effects of indoor air pollution on neurological health. Indoor air pollution exposure is particularly high in low- and middle-income countries, where people commonly burn solid fuels in the home for cooking.
The investigation included 142 mother-child pairs enrolled in a South African study. Using personal air samplers, the researchers measured particulate matter (PM) inside participants’ homes during the second trimester of pregnancy. They assessed DNA methylation in cord blood samples and later evaluated cognitive development in 2-year-olds. Using a statistical approach called high-dimensional mediation analysis, they searched for DNA with altered methylation levels that could underlie the effects of PM exposure on neurodevelopment.
They identified changes in methylation in 29 DNA regions and four genes that significantly mediated the association between PM and cognitive neurodevelopment. Importantly, several of those areas were related to biological pathways important in cognitive neurodevelopment and fetal brain development.
Findings suggest that changes in DNA methylation may drive the association between prenatal PM exposure and neurodevelopment. This study adds to the limited literature investigating this relationship, particularly in low- and middle-income countries.
Citation: Feil D, Abrishamcar S, Christensen GM, Vanker A, Koen N, Kilanowski A, Hoffman N, Wedderburn CJ, Donald KA, Kobor MS, Zar HJ, Stein DJ, Hüls A. 2023. DNA methylation as a potential mediator of the association between indoor air pollution and neurodevelopmental delay in a South African birth cohort. Clin Epigenetics 15:31.
(Megan Avakian is a science writer for MDB Inc., a contractor for the NIEHS Division of Extramural Research and Training.)