Preconception exposures of

Overview

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Key numbers

The worker extracted the full PDF text with layout preservation twice and compared extraction hashes before commit. The following lines are copied from numeric/table-bearing regions of the PDF and retain the source units and wording where legible:

• whose prevalence has dramatically increased in the last 50 years, and only ~2.7% of cases can
• of environmental stressors of varying nature from the moment of - DMSO (negative control) group: 0.1% dimethylsulfoxide
• interplay between life experiences and exposures that contribute - 5TBT group: 5 nM tributyltin (TBT) and 0.1% DMSO in
• • 50TBT group: 50 nM tributyltin and 0.1% DMSO in water
• • IAS group: 10 µg/L sodium meta(arsenite) (inorganic
• arsenic, iAs) and 0.1% DMSO in water and CD.
• multigenerational obesity (6–9, 22). iAs is a naturally occurring - TWD group: 0.1% DMSO in water and Total Western Diet
• adiposity and increased risk of type-2 diabetes in human (NOAEL) for TBT is 0.025 mg/Kg/day (27). 50 nM TBT in
• populations (24). Maternal preconception exposure to drinking water is equivalent to 0.005 mg/Kg/day, assuming an
• about potential epigenetic alterations associated with such lower than the NOAEL, respectively. We used 10 µg/L of inorganic
• diet 50% of the U.S. population takes, is an example of a lifestyle Low-fat CD and high-fat TWD have energy densities of 3.8 and
• metabolism disruptor (26). Although the separate exposure to these 4.4 Kcal/g, respectively, and 17.2 and 34.5% of their energy content
• three metabolism disruptors will not conveniently model the is provided by fat, respectively. TWD represents the diet 50% of U.S.
• hgdownload.soe.ucsc.edu/downloads.html#mouse) (31). We count tables for each of the 16 exposure versus control contrast
• base R functions and the data.table package (version 1.17) (41) for we calculated relative gene fractions as log10((x/n)/(X/N)), where x
• by 1 million. To rescale normalized counts to the same 0–1 range, Lep gene expressions in gWAT.
• We used R packages data.table (version 1.17) (41), ggplot2 calculated in the third step. Fifth, signed ranks for each subtraction
• chance (7, 8, 55–57). Recently, we have reformulated MCW tests to tests will perform a number of rearrangements equal to
• bias index (BI) that spans the range of 1 to -1, indicating that the ranked, with the lowest absolute difference receiving the lowest
• BI values always range from -1 to 1, comparing results from MCW calculating Pupper and Plower values as previously indicated.
• all MCW tests, we set max_rearrangements parameter to 10,000. and food consumption (Figure 1d) for either TBT exposure. While
• group), 50 nM TBT and CD (50TBT group), 10 µg/L sodium (meta) significantly higher body weights, lower fasting body weights,
• 16. Owen JA, Osmanović D, Mirny L. Design principles of 3D epigenetic memory data.table: extension of data.frame (2025). Available online at: https://CRAN.R-
• 65. Goodman CS, Kolodkin AL, Luo Y, Püschel AW, Raper JA. Unified nomenclature psychiatric origins for anorexia nervosa. Nat Genet. (2019) 51:1207–14. doi: 10.1038/

Methods (brief)

• commonly found in soil, dust, and water and in human samples
• together. We weighed F1 mice at weaning and weekly thereafter We weighed gWAT, iWAT, and liver samples harvested from
• Diabetes Care) with blood drawn from the mouse tails. At 12 weeks We submitted 50 µL of F1 plasma samples from euthanized
• minimize coagulation and collected cardiac blood samples in outside the standard curve range or that could not be
• samples at 5,000 x g for 10 minutes at 4°C to separate plasma. used uMCW tests to assess the significance of differences in plasma
• We weighed gWAT, iWAT, and liver samples and snap-frozen levels between exposure and control groups (Supplementary Data
• samples frozen for downstream analyses. Dissections were 4.5) (29) to perform Principal Component Analysis (PCA) on
• beaker atop a standard laboratory balance (Supplementary Data 6, manufacturer’s protocols. We submitted the RNA samples to the
• differences between exposure groups (5TBT, 50TBT, IAS, and 100 RNA samples (2 sexes x 2 tissues x 5 experimental groups x 5
• measures Monte Carlo-Wilcoxon (uMCW) tests (see Statistics approximately 30 million 150-bp paired reads per sample. We used
• represents cpm values for each gene and sample, and min(x) and
• autosomes and the X chromosome, and the file gene across samples, respectively.
• mapped it in at least 2 samples in each contrast and discarded non-
• quality, multiQC (version 1.27) (36) to generate multi-sample gene ranks (43).
• liver sample and isochore class associations (Supplementary
• Data 17). and normalized read counts for each sample as previously indicated.
• visualize expression patterns across samples of the 100,000 most class or any class, respectively, and n and N represent the number of
• samples and identified genes with the top 100,000 cumulative class or any class, respectively.

Implications

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Wiki pages this source may touch

• Fish — marine, non-predatory (sardines, anchovies, salmon, cod)
• Arsenic
• Tin

Verification notes

• Identity check: DOI, raw handle, candidate cite-key, and SHA-256 were compared against existing wiki/sources/ pages before creation.
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Update history

The five most recent substantive edits to this page, classified major (evidence or structure moved), correction (a published value or statement was wrong and has been fixed), or minor (narrative rewritten without changing the underlying evidence). Each description is derived from what the edit did to this page; the linked commit is the authoritative record, routine regeneration passes are excluded, and the full version history lives in git. When DOI minting comes online (see schema docs), each entry below will also link to a version-pinned DataCite DOI.