Abstract 148: Sex-Differences in Fetal Programming of Cardiomyopathy Induced by Hypertensive Disorders of Pregnancy in Mice
Bibliographic record
Abstract
Background: Hypertensive disorders reach one in ten pregnancies worldwide, significantly increasing rates of maternal and neonatal morbidity and mortality. Children born to hypertensive pregnancies can develop special clinical features that are consistent with a preterm or accelerated aging process with signs of cardiac remodeling as early as childhood. The aim of this study was to develop a new ultrasound imaging protocol to describe sex-differences in the fetal programming of cardiomyopathy in a genetic mice model of maternal hypertension and superposed pre-eclampsia. Methods and Results: We have performed fetal echocardiography imaging in n=4/group transgenic mice overexpressing human renin+angiotensinogen versus controls (C57BL/6) at 18.5 gestational days. Fetal images were adjusted by intracranial diameter as an intrauterine marker of fetal growth. Male and female offspring (n=8/group/sex) were followed by echocardiography up to 40 postnatal days. Data are average±SD. Fetuses of hypertensive mothers had thicker left ventricular (LV) walls (0.32±0.02 vs 0.45±0.04mm, P<.01) and more dilated chamber (0.82±0.02 vs 0.97±0.07mm, P<.01), with larger LV mass (3.2±0.4 vs 4.3±0.3mg, P<.001) compared to controls, which remained significant after adjusting for intracranial diameters. Into adulthood, male and female offspring of hypertensive mothers had greater LV mass (male: 88±19 vs 139±62mg, P<.01; female: 74±21 vs 104±27, P<.05) and wall thickness (male: 0.70±0.03 vs 0.95±0.22mm, P<.05; female: 0.63±0.15 vs 0.91±0.17mm, P<.05) compared to control offspring. However, females had additional LV chamber dilation (3.3±0.3 vs 3.9±0.4mm, P<.05) and reduced fraction of shortening (48±9 vs 33±4%, P<.01) compared to controls, indicating LV systolic dysfunction and cardiomyopathy only in in this offspring group but not in males. Conclusion: Our results demonstrate the feasibility of using fetal and postnatal echocardiography to evaluate the programming of cardiomyopathy in mice exposed to hypertensive pregnancy. In addition, we showed that fetal cardiac remodeling changes persisted into adulthood in offspring of hypertensive mothers, which in females has further progressed to an accelerated cardiomyopathy programming.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.008 | 0.002 |
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".