المؤلفون: Anastasia N. Freedman, Kyle Roell, Eiona Engwall, Catherine Bulka, Karl C. K. Kuban, Laura Herring, Christina A. Mills, Patrick J. Parsons, Aubrey Galusha, Thomas Michael O’Shea, Rebecca C. Fry

المصدر: International Journal of Molecular Sciences, Vol 24, Iss 19, p 14977 (2023)

مصطلحات موضوعية: metals, placenta, umbilical cord tissue, proteomics, preterm birth, sexual dimorphism, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: Prenatal exposure to toxic metals is associated with altered placental function and adverse infant and child health outcomes. Adverse outcomes include those that are observed at the time of birth, such as low birthweight, as well as those that arise later in life, such as neurological impairment. It is often the case that these adverse outcomes show sex-specific responses in relation to toxicant exposures. While the precise molecular mechanisms linking in utero toxic metal exposures with later-in-life health are unknown, placental inflammation is posited to play a critical role. Here, we sought to understand whether in utero metal exposure is associated with alterations in the expression of the placental proteome by identifying metal associated proteins (MAPs). Within the Extremely Low Gestational Age Newborns (ELGAN) cohort (n = 230), placental and umbilical cord tissue samples were collected at birth. Arsenic (As), cadmium (Cd), lead (Pb), selenium (Se), and manganese (Mn) concentrations were measured in umbilical cord tissue samples via ICP-MS/MS. Protein expression was examined in placental samples using an LC-MS/MS-based, global, untargeted proteomics analysis measuring more than 3400 proteins. MAPs were then evaluated for associations with pregnancy and neonatal outcomes, including placental weight and gestational age. We hypothesized that metal levels would be positively associated with the altered expression of inflammation/immune-associated pathways and that sex-specific patterns of metal-associated placental protein expression would be observed. Sex-specific analyses identified 89 unique MAPs expressed in female placentas and 41 unique MAPs expressed in male placentas. Notably, many of the female-associated MAPs are known to be involved in immune-related processes, while the male-associated MAPs are associated with intracellular transport and cell localization. Further, several MAPs were significantly associated with gestational age in males and females and placental weight in males. These data highlight the linkage between prenatal metal exposure and an altered placental proteome, with implications for altering the trajectory of fetal development.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/1422-0067/24/19/14977Test; https://doaj.org/toc/1661-6596Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/c863aadc204d44c4a0c3c0d944780645Test

المؤلفون: Julia E. Rager, Andrew Yosim, Rebecca C. Fry

المصدر: International Journal of Molecular Sciences, Vol 15, Iss 12, Pp 22374-22391 (2014)

مصطلحات موضوعية: arsenic, cadmium, environmental toxicant, epigenome, genome, glucocorticoid receptor, infectious disease, in utero, pathway, signal transduction, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: There is increasing evidence that environmental agents mediate susceptibility to infectious disease. Studies support the impact of prenatal/early life exposure to the environmental metals inorganic arsenic (iAs) and cadmium (Cd) on increased risk for susceptibility to infection. The specific biological mechanisms that underlie such exposure-mediated effects remain understudied. This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). Using CGEM an infectious disease gene (IDG) database was developed comprising 1085 genes with known roles in viral, bacterial, and parasitic disease pathways. Subsequently, datasets collected from human pregnancy cohorts exposed to iAs or Cd were examined in relationship to the IDGs, specifically focusing on data representing epigenetic modifications (5-methyl cytosine), genomic perturbations (mRNA expression), and proteomic shifts (protein expression). A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/15/12/22374Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/6f8cad2c2fef4c179f178d9681bf55cfTest

المؤلفون: Andrew Yosim, Julia E. Rager, Rebecca C. Fry

المصدر: International Journal of Molecular Sciences
Volume 15
Issue 12
Pages 22374-22391
International Journal of Molecular Sciences, Vol 15, Iss 12, Pp 22374-22391 (2014)

مصطلحات موضوعية: epigenome, Disease, 010501 environmental sciences, 01 natural sciences, Toxicogenetics, lcsh:Chemistry, Cohort Studies, Glucocorticoid receptor, Pregnancy, Risk Factors, glucocorticoid receptor, Gene Regulatory Networks, lcsh:QH301-705.5, Spectroscopy, Genetics, 0303 health sciences, environmental toxicant, General Medicine, 3. Good health, Computer Science Applications, Prenatal Exposure Delayed Effects, Female, Signal transduction, Glucocorticoid, signal transduction, medicine.drug, cadmium, infectious disease, Biology, Communicable Diseases, in utero, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Receptors, Glucocorticoid, medicine, Humans, Epigenetics, Physical and Theoretical Chemistry, Molecular Biology, Gene, genome, 030304 developmental biology, 0105 earth and related environmental sciences, pathway, Organic Chemistry, arsenic, Reproducibility of Results, Epigenome, lcsh:Biology (General), lcsh:QD1-999, Infectious disease (medical specialty), Immunology

الوصف: There is increasing evidence that environmental agents mediate susceptibility to infectious disease. Studies support the impact of prenatal/early life exposure to the environmental metals inorganic arsenic (iAs) and cadmium (Cd) on increased risk for susceptibility to infection. The specific biological mechanisms that underlie such exposure-mediated effects remain understudied. This research aimed to identify key genes/signal transduction pathways that associate prenatal exposure to these toxic metals with changes in infectious disease susceptibility using a Comparative Genomic Enrichment Method (CGEM). Using CGEM an infectious disease gene (IDG) database was developed comprising 1085 genes with known roles in viral, bacterial, and parasitic disease pathways. Subsequently, datasets collected from human pregnancy cohorts exposed to iAs or Cd were examined in relationship to the IDGs, specifically focusing on data representing epigenetic modifications (5-methyl cytosine), genomic perturbations (mRNA expression), and proteomic shifts (protein expression). A set of 82 infection and exposure-related genes was identified and found to be enriched for their role in the glucocorticoid receptor signal transduction pathway. Given their common identification across numerous human cohorts and their known toxicological role in disease, the identified genes within the glucocorticoid signal transduction pathway may underlie altered infectious disease susceptibility associated with prenatal exposures to the toxic metals iAs and Cd in humans.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8980e67505d595e3a6f29fda94ae9722Test
https://pubmed.ncbi.nlm.nih.gov/25479081Test