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 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) | 0.001 | 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".