Perinatal iron deficiency and a high salt diet cause long-term kidney mitochondrial dysfunction and oxidative stress
Bibliographic record
Abstract
AIMS: Perinatal iron deficiency (ID) alters developmental trajectories of offspring, predisposing them to cardiovascular dysfunction in later life. The mechanisms underlying this long-term programming of renal function have not been defined. We hypothesized perinatal ID causes hypertension and alters kidney metabolic function and morphology in a sex-dependent manner in adult offspring. Furthermore, we hypothesized these effects are exacerbated by chronic consumption of a high salt diet. METHODS AND RESULTS: Pregnant Sprague Dawley rats were fed either an iron-restricted or replete diet prior to and throughout pregnancy. Adult offspring were fed normal or high salt diets for 6 weeks prior to experimentation at 6 months of age. Blood pressure (BP) was assessed via indwelling catheters in anaesthetized offspring; kidney mitochondrial function was assessed via high-resolution respirometry; reactive oxygen species and nitric oxide were quantified via fluorescence microscopy. Adult males, but not females, exhibited increased systolic BP due to ID (P = 0.01) and high salt intake (P = 0.02). In males, but not in females, medullary mitochondrial content was increased by high salt (P = 0.003), while succinate-dependent respiration was reduced by ID (P < 0.05). The combination of perinatal ID and high salt reduced complex IV activity in the cortex of males (P = 0.01). Perinatal ID increased cytosolic superoxide generation (P < 0.001) concomitant with reduced nitric oxide bioavailability (P < 0.001) in male offspring, while high salt increased mitochondrial superoxide in the medulla (P = 0.04) and cytosolic superoxide within the cortex (P = 0.01). Male offspring exhibited glomerular basement membrane thickening (P < 0.05), increased collagen deposition (P < 0.05), and glomerular hypertrophy (interaction, P = 0.02) due to both perinatal ID and high salt. Female offspring exhibited no alterations in mitochondrial function or morphology due to either high salt or ID. CONCLUSION: Perinatal ID causes long-term sex-dependent alterations in renal metabolic function and morphology, potentially contributing to hypertension and increased cardiovascular disease risk.
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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 | 0.001 | 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) | 0.000 | 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".