Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics

Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics

Sdougkou et al_Supplementary Information_feature_filtering_tagging_MS2_ions_script.ipynb

Supplementary material to Sdougkou et al.,Phospholipid Removal for Enhanced Chemical Exposomics in Human Plasma.https://doi.org/10.1021/acs.est.3c00663</p

Sdougkou et al_Supplementary Information_common_features_script.ipynb

Supplementary material to Sdougkou et al.,Phospholipid Removal for Enhanced Chemical Exposomics in Human Plasma.https://doi.org/10.1021/acs.est.3c00663</p

Phospholipid removal for enhanced chemical exposomics in human plasma

The challenge of chemical exposomics in human plasma is the 1000-fold concentration gap between endogenous substances and environmental pollutants. Phospholipids are the major endogenous small molecules in plasma, thus we validated a chemical exposomics protocol with an optimized phospholipid-removal step prior to targeted and non-targeted liquid chromatography high-resolution mass spectrometry. Increased injection volume with negligible matrix effect permitted sensitive multiclass targeted analysis of 77 priority analytes; median MLOQ = 0.05 ng/mL for 200 μL plasma. In non-targeted acquisition, mean total signal intensities of non-phospholipids were enhanced 6-fold in positive (max 28-fold) and 4-fold in negative mode (max 58-fold) compared to a control method without phospholipid removal. Moreover, 109 and 28% more non-phospholipid molecular features were detected by exposomics in positive and negative mode, respectively, allowing new substances to be annotated that were non-detectable without phospholipid removal. In individual adult plasma (100 μL, n = 34), 28 analytes were detected and quantified among 10 chemical classes, and quantitation of per- and polyfluoroalkyl substances (PFAS) was externally validated by independent targeted analysis. Retrospective discovery and semi-quantification of PFAS-precursors was demonstrated, and widespread fenuron exposure is reported in plasma for the first time. The new exposomics method is complementary to metabolomics protocols, relies on open science resources, and can be scaled to support large studies of the exposome

Adult Exposure to Di-N-Butyl Phthalate (DBP) Induces Persistent Effects on Testicular Cell Markers and Testosterone Biosynthesis in Mice

Studies indicate that phthalates are endocrine disruptors affecting reproductive health. One of the most commonly used phthalates, di-n-butyl phthalate (DBP), has been linked with adverse reproductive health outcomes in men, but the mechanisms behind these effects are still poorly understood. Here, adult male mice were orally exposed to DBP (10 or 100 mg/kg/day) for five weeks, and the testis and adrenal glands were collected one week after the last dose, to examine more persistent effects. Quantification of testosterone, androstenedione, progesterone and corticosterone concentrations by liquid chromatography-mass spectrometry showed that testicular testosterone was significantly decreased in both DBP treatment groups, whereas the other steroids were not significantly altered. Western blot analysis of testis revealed that DBP exposure increased the levels of the steroidogenic enzymes CYP11A1, HSD3β2, and CYP17A1, the oxidative stress marker nitrotyrosine, and the luteinizing hormone receptor (LHR). The analysis further demonstrated increased levels of the germ cell marker DAZL, the Sertoli cell markers vimentin and SOX9, and the Leydig cell marker SULT1E1. Overall, the present work provides more mechanistic understanding of how adult DBP exposure can induce effects on the male reproductive system by affecting several key cells and proteins important for testosterone biosynthesis and spermatogenesis, and for the first time shows that these effects persist at least one week after the last dose. It also demonstrates impairment of testosterone biosynthesis at a lower dose than previously reported