131 DNA methylation profile in bovine fetal liver is affected by maternal vitamin and mineral supplementation during early gestation
Bibliographic record
Abstract
Abstract Early gestation is the critical period for successful pregnancy establishment. During this period, maternal nutrition affects fetal development with potentially long-lasting consequences on offspring performance. Despite the known effects of vitamins and minerals on embryonic development, supplementation is still not a widely adopted practice. Here we focused on the effects of maternal vitamin and mineral supplementation from pre-breeding to d 83 of gestation. We hypothesized that the DNA methylation pattern of genes involved with fetal hepatic metabolism and function would be altered in response to vitamin and mineral supplementation during early gestation. Sixteen Angus crossbred heifers (~16 mo of age) were randomly assigned to either a treatment (vitamin and mineral supplementation, VTM, n = 8) or control (corn-based carrier without supplementation, NoVTM, n = 8) group. Supplemented heifers received 0.45 kg •heifer-1•d-1 of to provide 113 g of vitamin-mineral premix (Purina Wind & Rain Storm All-Season 7.5 Complete, Land O’Lakes, Inc., Arden Hills, MN) from d 71 to 148 before breeding to d 83 of gestation. All heifers received 100% of NRC recommended nutritional requirements targeting 0.28 kg •heifer-1•d-1 of gain. The heifers were bred through artificial insemination following a 7-d Co-Synch + CIDR estrus synchronization protocol. All pregnant heifers were surgically ovariohysterectomized on d 83, and liver samples were collected from the fetuses. DNA methylation profiles from 16 fetuses (8 per treatment) were determined using Reduced Representation Bisulfite Sequencing (RRBS). The analysis was conducted using methylKit pipeline where data was normalized using principal components. We identified 794 differentially methylated cytosines (DMCs) for the control (NoVTM) vs VTM comparison. Most of the DMCs were found in introns followed by intergenic, promoter, and exonic regions. Among these DMCs, 60% (479) were hypermethylated and 40% (315) were hypomethylated, potentially regulating 739 nearby genes (FDR < 0.1). Biological processes over-represented by these genes included transport of ions through voltage gated channels (KCNK13, KCNT1, CACNA1B, KCNK9, LRRC55, KCNAB2, CACNA1S, KCNJ2, CACNG5, CLIC5, TPCN2, KCNQ1), which may be associated to pregnancy establishment by inducing pregnancy-associated relaxation and uterine artery dilatation. Some genes associated with structural development were also regulated by VTM supplementation (i.e., TIAM1, COL18A1, DYSF, BMP10, RXRA, EHMT1, COL4A2, PLEC, ZFAT, MTMR2, NAV1, ANHX, ACACB, and LIMK2). Collectively, these results suggest that periconceptual maternal vitamin and mineral supplementation affects the methylation pattern and potentially regulates the expression of genes involved in fetal liver development and ion transport.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".