USA: Newborn metabolomic signatures of maternal PFAS exposure and reduced length of gestation

There are more than 7 million PFAS and over 21 million fluorinated compounds listed in PubChem (2023).
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USA: Newborn metabolomic signatures of maternal PFAS exposure and reduced length of gestation

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Taibl KR, Dunlop AL, Barr DB, Li YY, Eick SM, Kannan K, Ryan PB, Schroder M, Rushing B, Fennell T, Chang CJ, Tan Y, Marsit CJ, Jones DP, Liang D - "Newborn metabolomic signatures of maternal per- and polyfluoroalkyl substance exposure and reduced length of gestation" Nat Commun 14(1):3120 (2023) doi: 10.1038/s41467-023-38710-3
https://www.nature.com/articles/s41467-023-38710-3

Abstract:

Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid [PFOA] and perfluorohexane sulfonic acid [PFHxS] concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States.

NOTE:

1. PFOA and PFHxS have long been shown to influence thyroid hormone activity.
2. Thyroid hormone regulates metabolism.
3. Thyroid status is closely associated with gestation length/preterm birth (PTB).
4. Thyroid status is more sensitive in blacks. (Lower "normal" TSH levels").
5. Both inorganic and organic fluorides are associated with PTB.


Piras C, Arisci N, Poddighe S, Liggi S, Mariotti S, Atzori L - "Metabolomic profile in hyperthyroid patients before and after antithyroid drug treatment: Correlation with thyroid hormone and TSH concentration" Int J Biochem Cell Biol 93:119-128 (20217) doi: 10.1016/j.biocel.2017.07.024. Epub 2017 Aug 4
https://www.sciencedirect.com/science/a ... 2517301875
"This study shows that metabolomic profile is deeply influenced by hyperthyroidism and this alteration persists after normalization of thyrotropin (TSH) and free thyroid hormone (FT3, FT4) concentration."

Piras C, Pibiri M, Leoni VP, Balsamo A, Tronci L, Arisci N, Mariotti S, Atzori L - "Analysis of metabolomics profile in hypothyroid patients before and after thyroid hormone replacement" J Endocrinol Invest 44(6):1309-1319 (2021) doi: 10.1007/s40618-020-01434-y
https://link.springer.com/article/10.10 ... 20-01434-y
"1H NMR-based metabolomics profiling of patients with newly diagnosed hypothyroidism (HypoT0) showed significantly higher levels of citrate, creatinine, glycerol, myo-inositol and serine, and lower levels of proline and taurine compared to controls...These results suggest that metabolic changes in the patients with hypothyroidism may persist after normalization of serum levels of FT3, FT4, and TSH, which currently represent the gold standard in laboratory testing for diagnosis and evaluation of thyroid pathology."

Jaber MA, Benabdelkamel H, Dahabiyeh LA, Masood A, AlMalki RH, Musambil M, Alfadda AA, Abdel Rahman AM - "The metabolomics approach revealed a distinctive metabolomics pattern associated with hyperthyroidism treatment" Front Endocrinol (Lausanne) 13:1050201 (2022). doi: 10.3389/fendo.2022.1050201
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9685425/
"The medium-chain acylcarnitines, octanoylcarnitine, and decanoylcarnitine, previously found to rise in hyperthyroid patients, were among the down-regulated metabolites, suggesting that their reduction could be a possible biomarker for monitoring euthyroid restoration. Kynurenine is a downregulated tryptophan metabolite, indicating that the enzyme kynurenine 3-hydroxylase, inhibited in hyperthyroidism, is back functioning. L-cystine, a cysteine dimer produced from cysteine oxidation, was among the down-regulated metabolites, and its accumulation is considered a sign of oxidative stress, which was reported to accompany hyperthyroidism; L-cystine levels dropped, this suggests that the plasma level of L-cystine can be used to monitor the progress of euthyroid state restoration...The plasma metabolome of patients with hyperthyroidism before and after treatments revealed differences in the abundance of several small metabolites. Our findings add to our understanding of hyperthyroidism’s altered metabolome and associated metabolic processes and shed light on acylcarnitines as a new biomarker for treatment monitoring in conjunction with thyroxine and thyroid-stimulating hormone."

Jansen HI, Bruinstroop E, Yen PM - "Metabolomics to Assess Thyroid Hormone Status?" J Clin Endocrinol Metab 108(3):e36-e37. doi: 10.1210/clinem/dgac655 (2023)
https://academic.oup.com/jcem/article-a ... 36/6825703
"Several associations between metabolic biomarkers and TH status were reported previously and suggested that it might be possible to establish serum metabolic panels for thyroid diseases. In this connection, a serum panel combining several biomarkers recently was proposed as a potential tool to assess TH status in L-T4-treated patients."
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