Late Gestation Exposure to PolyI:C‐Induced Maternal Immune Activation Results in Sex‐Dependent Antiviral Responses in Rat Placenta
Bibliographic record
Abstract
Introduction Viral infections are a major cause of pregnancy‐related complications and can lead to neurodevelopmental deficits in offspring. Viral infections stimulate maternal immune activation (MIA), which disrupts the delicate immune balance required for pregnancy. The placenta is a temporary organ that forms the interface between mom and baby during pregnancy and provides nutrition and protection for the developing fetus. Placental responses to MIA, and how MIA alters placental function, are not well understood. Polyinosinic:polycytidylic acid (PolyI:C), a synthetic double‐stranded RNA and viral mimetic elicits MIA in rodent models. PolyI:C‐induced MIA is sufficient to cause neurobehavioural consequences in offspring, with male offspring typically exhibiting more severe outcomes than female offspring. Objective The aim of this project was to elucidate how MIA affects the immunological profiles of the nascent male and female placenta and brain from a late prenatal PolyI:C stimulation. Hypothesis We hypothesize that injection of PolyI:C into pregnant rats at late gestation will induce antiviral responses in the placenta and fetal brain, and these responses will differ between male and female fetuses. Methods To test this hypothesis , pregnant Sprague‐Dawley rats were injected intravenously with 4 mg/kg PolyI:C (N = 5) or saline (N = 4) on GD18.5. Five hours after injection, placentas and fetal brains were collected. Quantitative RT‐PCR was used to measure expression of various genes associated with antiviral responses (e.g., Ifna , Il6 , Il1a , Il1b , Tnfa , Ido1 , Cxcl10 , Rsad2 , Cxcl11 , Ccl5 , and Tlr3 ) in the placenta. A Student’s t ‐test was used to compare differences between two means, and a two‐way analysis of variance, followed by Sidak’s post‐hoc analysis was used to compare differences between treatments and sexes. Means were considered statistically significant when P ≤ 0.05. Results PolyI:C‐treated male placentas (n = 9) showed significantly higher levels of Rsad2 (2.4‐fold), Ifna (2.8‐fold), Mx1 (9.4‐fold), and Cxcl10 (23.3‐fold) compared to saline‐treated male placentas (n = 8; P ≤ 0.05). PolyI:C‐treated female placentas (n = 10) showed a significant upregulation of Cxcl10 (25.4‐fold) and Mx1 (11.4‐fold), as well as of Cxcl11 (19.8‐fold) and Tnfa (2.3‐fold) compared to saline‐treated female placentas (n = 8; P ≤ 0.05). Among PolyI:C‐treated samples, male placentas showed significantly increased expression of Ifna when compared to female placentas (2.8‐fold, P ≤ 0.05). Conclusion Our results show that PolyI:C‐induced MIA at late gestation stimulates a robust antiviral response in the placenta, including higher levels of Ifna in male placentas than female placentas. Significance Future work will characterize PolyI:C‐induced antiviral and sex‐dependent responses in fetal brains. Overall, this research will provide further insight into MIA‐induced susceptibility to pregnancy complications and neurodevelopmental outcomes.
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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 | 0.001 | 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 | 0.001 |
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".