Combining information on chemical exposures and social stressors reveals disproportionate burden

Researchers funded by NIEHS integrated information on chemical exposures and self-reported social stressors to reveal disproportionate exposure and stress burdens that may underly disparities in health. Although certain groups are more likely to be exposed to environmental, psychological, and social stressors, few studies have examined combined exposure to environmental toxicants and psychosocial stress.

For their study, the team looked at 97 women, who were six months postpartum, from the Brain and Early Experience cohort in North Carolina. The women wore silicone wristbands for one week as a simple and noninvasive tool to collect exposure data on 110 environmental chemicals. Then, participants reported different types of social stress, such as experiences of racism, co-parenting, or economic stress, using eight questionnaires. With advanced statistical techniques, the team evaluated associations among chemical exposure, demographic characteristics, and social stress.

The researchers reported co-occurring patterns in exposures largely based on chemical class, with phthalates representing the highest exposure and polychlorinated biphenyls the lowest. The team also identified differential exposure across racial groups, with diethyl phthalate, triphenyl phosphate, and tris(3,5-dimethyl phenyl) phosphate being measured at higher levels in Black participants compared with White participants. After integrating social stressor profiling with chemical exposure data, the team identified a particularly vulnerable subset of participants in which high chemical exposure burden coincided with high experiences of racism and economic stress.

According to the authors, these findings point to the need to investigate sources of differential exposure and how these combined stressors may contribute to disparities in maternal and child health. They further note that both chemical and social stressors should be considered and integrated when evaluating the exposome. (AL)

Citation: Hickman E, Frey J, Wylie A, Hartwell HJ, Herkert NJ, Short SJ, Mills-Koonce WR, Fry RC, Stapleton HM, Propper C, Rager JE. 2024. Chemical and non-chemical stressors in a postpartum cohort through wristband and self report data: Links between increased chemical burden, economic, and racial stress. Environ Int 191:108976.

Phthalate exposure before conception can affect gene expression in sperm

A study funded by NIEHS revealed that exposure to phthalates before a couple conceives can alter gene expression in sperm, potentially affecting reproductive success. Phthalates are ubiquitous pollutants in the environment; however, the mechanisms of phthalate-associated reproductive disorders in men are not fully understood. This study is one of the largest to date to provide mechanistic links between phthalate exposure and changes in sperm.

The team explored associations between phthalate exposure before conception and sperm DNA methylation — an epigenetic change that alters gene expression without affecting the DNA sequence — among 697 men from three prospective reproductive cohorts. Before conception, the researchers measured 18 phthalate and two phthalate alternative metabolites in urine samples and DNA methylation in sperm. Then, they performed a meta-analysis on results from all three cohorts.

In total, the team identified nearly 8,000 differentially methylated regions associated with urinary phthalates and phthalate replacements. Of the 20 phthalates and alternative phthalate metabolites analyzed, MBzP was associated with the highest number of sperm differentially methylated regions in both individual cohorts and in the meta-analysis. Most regions were positively associated with phthalate metabolite concentrations and were enriched in genes associated with spermatogenesis, response to hormones and their metabolism, embryonic organ development, and developmental growth.

According to the authors, these findings highlight how DNA methylation patterns acquired during sperm production and before conception are a sensitive window of development that may be influenced by environmental exposures. Large-scale epidemiological studies are needed to examine the relationship between these DNA methylation patterns and reproductive outcomes, such as fertilization, embryo development, and child growth and development, they noted. (AL)

Citation: Nowak K, Oluwayiose OA, Houle E, Maxwell DL, Sawant S, Paskavitz A, Ford JB, Minguez-Alarcon L, Calafat AM, Hauser R, Pilsner JR. 2024. Urinary concentrations of phthalate and phthalate alternative metabolites and sperm DNA methylation: A multi-cohort and meta-analysis of men in preconception studies. Environ Int 192:109049.

PCB exposure alters gene expression in the brain

Exposure to a mixture of polychlorinated biphenyls (PCBs) can harm the brains of female mice, according to a study funded by NIEHS. The results shed light on how PCB exposure directly and indirectly affects brain health.

PCBs are a class of chemicals that were once produced for use in a variety of applications, including in electrical equipment and construction materials. They are still inadvertently produced during the manufacturing of some consumer products, such as dyes and pigments. When PCBs are absorbed by the body, liver enzymes may convert them into hydroxylated PCBs, which can have different properties than the original compounds.

Groups of mice were fed different doses of a human-relevant PCB mixture for seven weeks before scientists measured PCB and hydroxylated PCB levels in mouse brain, liver, and serum. They also performed RNA sequencing on several brain regions and the liver to examine how PCB exposure affected gene function.

Different types of PCBs from the mixture were present in similar dose-dependent amounts throughout the body. However, hydroxylated PCB levels were much lower in the brain compared to the liver and serum. In addition, PCB exposure in the brain changed the expression of genes associated with neurodevelopmental and neurodegenerative diseases, whereas PCBs and hydroxylated PCBs in the liver activated pathways related to drug metabolism.

According to the authors, these findings highlight how PCB exposure affects different parts of the body and enhance understanding about the mechanisms behind PCB toxicity, which has important implications for human health. (MZ)

Citation: Bullert AJ, Wang H, Valenzuela AE, Neier K, Wilson RJ, Badley JR, LaSalle JM, Hu X, Lein PJ, Lehmler HJ. 2024. Interactions of polychlorinated biphenyls and their metabolites with the brain and liver transcriptome of female mice. ACS Chem Neurosci 15(21):3991-4009.

First of its kind study reveals link between PFAS, kidney function, and gut health

PFAS exposure may harm kidney health by disrupting bacteria in the gut microbiome, NIEHS-funded researchers found. According to the authors, this exploratory study is the first to analyze the connection among PFAS exposure, gut health, and kidney function.

The researchers measured PFAS levels and metabolites in the blood of 78 young adults from the Southern California Children’s Health Study, a multi-ethnic cohort of individuals at high risk for metabolic diseases. The team also used DNA sequencing to analyze gut bacterial composition. At a follow-up appointment four years later, they checked the participants’ kidney function by evaluating how well the kidneys filtered waste, a measurement known as estimated glomerular filtration rate (eGFR). Lower eGFRs indicate poorer kidney function.

The team found that higher PFAS exposure was associated with a 2.4% reduction in eGFR. Higher PFAS exposure was linked with increased levels of inflammatory metabolites and reduced the levels of anti-inflammatory metabolites in participants’ blood. Higher PFAS exposure was also associated with reduced levels of beneficial gut bacteria.

According to the authors, these findings suggest that targeting the gut microbiome could help protect against PFAS-related kidney damage. (MZ)

Citation: Hampson HE, Li S, Walker DI, Wang H, Jia Q, Rock S, Costello E, Bjornstad P, Pyle L, Nelson J, Gilliland FD, Chen Z, Aung M, Chatzi L, Conti DV, Alderete TL, Goodrich JA. 2024. The potential mediating role of the gut microbiome and metabolites in the association between PFAS and kidney function in young adults: A proof-of-concept study. Sci Total Environ 954:176519.