Contrasting Effects of Phosphatidylcholine and Betaine Supplementation on Embryonic Development in a Mouse Model of the MTHFD1 R653Q Variant
Bibliographic record
Abstract
Background Folate and choline are interconnected nutrients important for embryonic development. Genetic variants in folate enzymes, such as MTHFD1 R653Q (c.1958 G>A, rs2236225), may increase dietary choline requirements. Objective To evaluate impact of phosphatidylcholine or betaine supplementation on embryonic development and maternal choline metabolism in the Mthfd1S +/- mouse model for the MTHFD1 653QQ genotype. Methods Female Mthfd1S +/+ (WT) and Mthfd1S +/- (HET) mice were fed amino acid-defined control (Ctrl), phosphatidylcholine-supplemented (PtdCho) or betaine-supplemented (BTN) diets for 4-6 weeks before mating and during pregnancy (18-33 mice/group). Ctrl contained 2.5 g choline bitartrate/kg diet (based on AIN-93G). Supplemented diets contained additional phosphatidylcholine or betaine to obtain the molar equivalent of three times the free choline of Ctrl. Embryos were examined for anatomical developmental delays and morphological defects at embryonic day 10.5. One-carbon metabolites (homocysteine, choline, betaine, methionine, cystathionine, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH)) were measured in maternal plasma and liver by LC-MS/MS. MTHFR protein in maternal liver was assessed by Western blot. Data were analyzed by binary logistic regression or 2-way ANOVA. Results PtdCho increased developmental delays, versus Ctrl, in litters of WT (170%) and HET (125%) mothers ( P diet <0.05). BTN decreased delays 53% versus Ctrl in HET mother’s litters ( P diet(HET) <0.05). Defects decreased 71% in BTN-fed HET mother’s litters compared to WT ( P <0.05). BTN increased total pregnancy losses 360% ( P diet <0.01); PtdCho had no effect. Both diets decreased maternal plasma homocysteine (30-50%, P diet <0.05), increased liver betaine (220-290%, P diet <0.0001) and decreased SAM/SAH (WT: 20-30%, HET: 48-61%, P diet <0.05). MTHFR protein expression decreased 25% in PtdCho maternal liver ( P diet <0.01). Conclusions Phosphatidylcholine and betaine supplementation had contrasting effects on reproductive outcomes. Phosphatidylcholine increased developmental delays. Betaine reduced delays and defects in the Mthfd1S +/- mouse model, but may impair establishment of pregnancy. The timing, form and dosage of choline supplementation may be important and require further investigation.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".