Exposome profiling uncovers pollutants tied to male infertility

A new approach for screening environmental contaminants revealed certain organic pollutants can negatively affect male fertility, according to a study funded by NIEHS. The findings provide clues to why global infertility rates are rising.

Some substances, like chemicals used in plastics and those that occur in air pollution, are known to cause reproductive harm. Identifying others that may affect fertility is challenging because people are exposed daily to thousands of chemicals, many of which have no reproductive toxicity data. In addition, current analytical methods can only measure a few chemicals at a time and often require large sample sizes.

To overcome these limitations, the researchers analyzed a wide range of pollutants for male reproductive toxicity. They then evaluated the chemicals’ effect on sperm health by measuring sperm concentration; motility, or the ability of sperm to move effectively; and the total number of motile sperm.

Using semen samples from 100 individuals, they applied high-resolution mass spectrometry to analyze the samples for organic pollutants — or chemicals they expected to be present — as well as untargeted, or unidentified, organic pollutants. The team then combined a machine-learning technique with statistical analysis to evaluate how these chemicals influence reproductive health.

Among the targeted pollutants, etridiazole, a common fungicide, was strongly associated with lower sperm count and motility. Among the untargeted chemicals, the team discovered a substance linked to reduced motile sperm. Further analysis determined the substance was N-nitrosodiethylamine, which can be a drinking water contaminant due to its wide range of industrial applications.

This is the first human study to show that etridiazole and N-nitrosodiethylamine may harm male reproductive health in humans, according to the authors. They noted that their approach provides an efficient method for screening hundreds of exposures without needing a large sample size.

Citation: Wu H, Kalia V, Manz KE, Chillrud L, Dishon NH, Jackson GL, Dye CK, Orvieto R, Aizer A, Levine H, Kioumourtzoglou MA, Pennell KD, Baccarelli AA, Machtinger R. 2024. Exposome profiling of environmental pollutants in seminal plasma and novel associations with semen parameters. Environ Sci Technol 58(31):13594-604.

Microbe commonly found in the environment can destroy specific PFAS

Researchers funded by NIEHS identified a type of bacteria that can destroy specific PFAS. Called Acetobacterium, the microorganisms are commonly found in wastewater environments throughout the world and could potentially be optimized and used as a cost-effective and environmentally friendly approach to remediate sites contaminated with the persistent chemical.

PFAS are a large class of synthetic chemicals used in products like nonstick cookware and firefighting foams. Their strong carbon-fluorine bonds resist degradation, allowing the chemicals to persist in the environment and accumulate in organisms.

The research team exposed various types of bacteria to a specific PFAS called PFMeUPA to see whether they could break the strong carbon-fluorine bonds through a process called defluorination. Results showed that some Acetobacterium species successfully defluorinated the chemical. Next, the scientists conducted further tests and used computer modeling to uncover the mechanisms involved in defluorination. They determined that enzymes involved in the caffeate-reduction complex played a crucial role in cleaving the carbon-fluorine bonds. The caffeate-reduction complex alters the distribution of negative charge in molecules and breaks carbon-carbon double bonds, allowing bacteria to then break the carbon-fluorine bonds.

The findings could help bioengineers improve these enzymes so the bacteria can target other PFAS compounds, according to the authors. The team is now exploring more novel defluorinating bacteria based on the genetic markers identified from this study.

Citation: Yu Y, Xu F, Zhao W, Thoma C, Che S, Richman JE, Jin B, Zhu Y, Xing Y, Wackett L, Men Y. 2024. Electron bifurcation and fluoride efflux systems implicated in defluorination of perfluorinated unsaturated carboxylic acids by Acetobacterium spp. Sci Adv 10(29):eado2957.

New framework links prenatal mercury exposure to liver disease

Using a novel framework that leverages multi-omics, NIEHS-funded researchers found a link between prenatal mercury exposure and an increased risk of developing liver disease later in life. Multi-omics combines analytical techniques from different branches of biology to gain deeper understanding of organisms.

Mercury, a toxic heavy metal, can affect various biological mechanisms and increase the risk of metabolic dysfunction-associated fatty liver disease (MAFLD), which is the leading cause of liver disease in children and can cause severe health issues later in life. To shed new light on the molecular pathways that may connect mercury exposure with disease, as well as related biomarkers and high-risk groups, the researchers leveraged a new multi-omics framework.

The study involved 420 mother-child pairs from the Human Early Life Exposome project in Europe. Researchers measured mercury levels in the mothers’ blood during pregnancy and assessed a MAFLD biomarker, CK-18, in the children’s blood when they were 6-10 years old. Then they analyzed five types of biological data — DNA changes, gene activity, microRNA, proteins, and metabolites — for connections between mercury exposure and biological effects.

Statistical analysis showed that higher prenatal mercury levels were linked to increased CK-18 levels in children. Elevated CK-18 levels were associated with 10 biological effects, including changes in some regions in the DNA sequence and the activity of specific genes. The team also found changes in biological pathways related to how the body signals inflammation and how liver cells respond, among others, which may explain how mercury exposure leads to MAFLD. In addition, they identified a group of children at the greatest risk of developing severe health outcomes later in life based on their exposure levels, genetic markers, and MAFLD risk.

According to the authors, this new framework can be used to guide future precision health research, which aims to improve disease prevention using multi-omics data.

Citation: Goodrich JA, Wang H, Jia Q, Stratakis N, Zhao Y, Maitre L, Bustamante M, Vafeiadi M, Aung M, Andrušaitytė S, Basagana X, Farzan SF, Heude B, Keun H, McConnell R, Yang TC, Siskos AP, Urquiza J, Valvi D, Varo N, Småstuen Haug L, Oftedal BM, Gražulevičienė R, Philippat C, Wright J, Vrijheid M, Chatzi L, Conti DV. 2024. Integrating multi-omics with environmental data for precision health: a novel analytic framework and case study on prenatal mercury induced childhood fatty liver disease. Environ Int 190:108930.

High exposure to plasticizer chemicals found in urban California

NIEHS-funded researchers reported high levels of toxic chemicals called plasticizers in residents of urban areas in California. The study is one of the first to explore such exposures in population-dense areas.

Plasticizers are synthetic chemicals used to add flexibility to consumer products, including furniture, car upholstery, and personal care items. Although previous California monitoring programs have focused on plasticizers called ortho-phthalates, which are being phased out due to health and environmental concerns, less attention has been given to their replacements, called non-ortho-phthalates. In addition, most research has mainly focused on rural, agricultural areas of the state.

The study included two groups of undergraduate students from the University of California, Riverside, one in 2019 and the other in 2020. These students commuted from various urban areas in Southern California. Both groups wore silicone wristbands for five days and completed questionnaires about their daily activities. The wristbands, designed by another team of NIEHS-funded researchers, collect data on chemical exposures in the air.

Wristband data revealed that the individuals’ exposure to ortho-phthalate and non-ortho-phthalate plasticizers was widespread and consistent over time and across different regions of Southern California, with concentrations ranging from approximately 100,000 to 1,000,000 nanograms per gram. Three specific chemicals — DiNP, DEHP, and DEHT — made up about 94-97% of the detected substances. The ortho-phthalates DiNP and DEHP are listed as toxic under Proposition 65, a California law that helps consumers make informed decisions about products. Limited toxicity data on DEHT, a non-ortho phthalate, exists.

According to the authors, the results suggest that urban populations in California are being exposed to potentially harmful levels of plasticizers, despite efforts to phase out ortho-phthalates. Because the toxicity of replacement chemicals remains poorly understood, exposures to DEHT raise concerns about health risks.

Citation: Reddam A, Herkert N, Stapleton HM, Volz DC. 2024. Silicone wristbands reveal ubiquitous human exposure to ortho-phthalates and non-ortho-phthalate plasticizers in Southern California. Environ Res 258:119465.