Sex-dependent biobehavioural responses to transgenerational maternal stress: evidence of stress resilience and vulnerability in the F3 generation
Bibliographic record
Abstract
Maternal prenatal stress can determine stress resilience and vulnerability of future generations. However, the extent to which the biological sex of the descendants determines the response to ancestral stress is not fully understood. In this study, neurohormonal responses and exploratory and anxiety-like behaviours were examined in third-generation (F3) male and female rats born to non-stressed and transgenerationally stressed lineages, where maternal stress was induced only in pregnant females of the ancestral F0 generation. While ancestral stress in F3 females did not alter hypothalamic-pituitary-adrenal (HPA) axis activity, F3 males born to F0 stressed mothers exhibited HPA axis hyperactivity compared to non-stressed males. By contrast, females revealed significantly higher corticosterone levels than males. Moreover, ancestral stress elevated concentrations of the cytokines interleukin-1β (IL-1β) and IL-10 exclusively in females. Ancestral maternal stress also produced task-specific differences in depressive- and anxiety-like symptoms in the F3 generation, particularly in females. Specifically, F3 female behaviour within the open field and elevated plus maze tasks was more affected by ancestral maternal stress than that of F3 males. Supported by correlational analysis, the findings demonstrate that F3 female offspring are more sensitive than males to the neuroimmunological and behavioural impacts of maternal prenatal stress, despite the absence of elevated HPA axis activity. In contrast, males primarily responded with HPA axis activity upregulation, which compounded effects on their behavioural profile. The present study supports the notion that maternal stress, across generations, is likely to epigenetically programme sex-specific behavioural, physiological, and immunological phenotypes in remote offspring, with particular vulnerability in females.
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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 | 0.001 |
| 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".