Methylenetetrahydrofolate reductase and dietary folate: developmental impact and gene regulation
Bibliographic record
Abstract
Maternal genetic and nutritional influences have a vast impact on developmental outcome. In particular, disturbances in folate metabolism have been well-studied since the finding that dietary folate dramatically reduces the incidence of neural tube defects (NTD). A mild deficiency in the folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR), and altered dietary folate are clearly associated with NTD, however, their effects on other congenital defects and pregnancy complications are not conclusive. In this thesis, the impact of MTHFR deficiency and altered dietary folate on embryonic and placental development were investigated in our mouse model of MTHFR deficiency. Additional studies characterizing Mthfr promoter activity in vitro and in vivo will help better understand the role of MTHFR deficiency in the associated human disorders. Maternal MTHFR and folate deficiencies increased embryonic delay and growth retardation and resulted in a low incidence of embryonic defects at 10.5 days post coitum (dpc). Folate deficiency increased embryonic loss and abnormal placental phenotypes, including abruption and disturbed patterning of placental layers. Folate-deficient placentae also had decreased ApoA-I staining suggesting that a deficiency in cholesterol may contribute to the embryonic and placental abnormalities observed. A high folate diet increased embryonic delay, growth retardation, and non-significantly of embryonic defects, at 10.5 and/or 14.5 dpc. Maternal MTHFR deficiency appeared to improve some of the adverse outcomes due to high dietary folate. Characterization of the two Mthfr promoters revealed temporal and tissue-specific regulation of Mthfr. The downstream promoter had specific activity in 10.5-dpc embryos and placentae, while the upstream promoter had strongest activity in cultured neuronal cells and in the adult brain and testis. Activity from both promoters was observed in neonatal epididymis. NF-κB was identifi
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.006 | 0.001 |
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".