Conserved <scp>DNA</scp> methylation signatures in the prefrontal cortex of female newborn and juvenile guinea pigs following antenatal betamethasone exposure
Bibliographic record
Abstract
Antenatal corticosteroids (ACS) improve perinatal survival when there is a risk of preterm birth. Although evidence suggests an increased risk of developing neurobehavioural disorders in exposed offspring, the mechanisms involved remain largely unknown. Here, we investigated the DNA methylation patterns in the prefrontal cortex (PFC) of ACS-exposed guinea pig offspring. We hypothesized that differential methylation will be evident at both newborn and juvenile ages. In two separate cohorts, pregnant guinea pigs were administered a subcutaneous injection of saline or betamethasone (1 mg/kg) on gestational days 50/51 to mimic a single course of ACS. The gDNA was isolated from the PFC of term-born female offspring on postnatal day 1 (PND1, n = 7/group) and PND14 (n = 6-7/group) to identify differentially methylated CpG sites (DMCs) using reduced representative bisulphite sequencing. In the PND1 PFC, 1521 DMCs, annotating 144 genes were identified following ACS. Identified genes are involved in pathways regulating 'developmental cellular process'. In the PND14 PFC, 776 DMCs representing 46 genes were identified and enriched in 'synaptic signalling' pathways. Though no individual DMCs were identified at both PND1 and PND14, differential methylation was consistently observed at the binding sites of transcription factors PLAGL1, TFAP2C, ZNF263 and SP1 at both ages. We have established that ACS exposure leads to altered DNA methylation in the PFC of guinea pig offspring at both newborn and juvenile ages. Notably, a unique methylation signature was consistently observed at four key transcription factor binding sites at both post-natal time points. These changes may predispose the development of altered neurobehavioural phenotypes that have been described in ACS-exposed offspring.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| 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) | 0.000 | 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 teacher head, 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".