Androgen Aggravates Chorioamnionitis-Induced White Matter Brain Injury and Neurobehavioral Impairments in Males
Bibliographic record
Abstract
Introduction: Group B Streptococcus (GBS) colonization leads to placental infection and inflammation, known as chorioamnionitis (CA). Fetal exposure to CA is linked to elevated risks of neurobehavioral impairments in offspring, including autism spectrum disorder, which is more prominent in males than females. In our preclinical model of GBS-induced CA, males exhibited heightened placental inflammation compared to females, correlating with more severe subsequent neurobehavioral impairments. We hypothesize that androgens upregulate the placental immune response in male fetuses, potentially contributing to GBS-induced autistic-like traits in male offspring. Our previous findings demonstrated that there were reduced pro-inflammatory cytokines and polymorphonuclear cell infiltration in flutamide (androgen receptor antagonist) plus GBS-infected compared to vehicle plus GBS-infected placenta. In this study, we investigated the effect of end gestational androgen blockade on brain injury patterns and neurobehavioral outcomes in offspring in utero exposed to GBS CA. METHODS: Lewis dams received daily injections of vehicle or flutamide from gestational day (G) 18-21, followed by saline or inactivated GBS injections from G19 to 21. Behavioral assessments were conducted from postnatal day (P) 9-40 and brains were dissected on P50. RESULTS: Behavioral assessments revealed impaired social interactions in CA-exposed versus unexposed male rats. These impairments were not observed in flutamide-treated rats. Histological analysis of forebrains at P50 showed lateral forebrain ventricle enlargement and reduced periventricular white matter thickness, namely the corpus callosum and external capsule in offspring exposed to CA contrasting with an improvement in these outcomes observed in flutamide treated rats. Exposure to CA reduced the density of CC-1+ oligodendrocytes in the external capsule whereas flutamide mitigated this reduction in offspring at P50. CONCLUSION: These findings suggest a significant role for androgens in the skewed sex ratio observed in developmental impairments resulting from perinatal inflammation, underscoring the need for personalized sex-specific neuroprotective therapies. .
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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) | 0.001 | 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) | 0.004 | 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".