Virus-Specific Alterations in Placental Structure and Transporter Expression Following Maternal Arbovirus Infection
Bibliographic record
Abstract
We hypothesized that arboviruses impair the placental expression of key functional markers implicated in fetal brain development. Singleton placentae (n = 54) affected by chikungunya (CHIKV, n = 12), dengue (DENV, n = 8), zika (ZIKV, n = 15), or healthy controls (HC, n = 15) were analysed. Immunohistochemical quantification of key transporter systems, cell turnover markers, and signalling pathways related to extracellular matrix remodelling, vascular maintenance, and nutrient sensing was undertaken. Maternal age and BMI were lower in CHIKV/ZIKV, whereas birth weight was reduced in DENV pregnancies compared with HC. CHIKV/ZIKV exhibited reduced syncytiotrophoblast area, CHIKV/DENV showed reduced syncytial knot area, whereas DENV showed increased fetal blood vessel and reduced connective tissue areas. Histopathology detected predominantly mild vascular and stromal lesions across groups, with DENV placentae exhibiting moderate congestion in 100% of cases. Decreased expression of P-gp, BCRP, ABCA1 and SNAT2 were detected in all groups. CHIKV/ZIKV also exhibited decreased GLUT1, while ZIKV showed reduced SNAT1 expression. MCT8 expression was significantly elevated in CHIKV. Placental Ki-67 was increased in CHIKV/ZIKV, indicating altered trophoblast turnover. VEGFB expression was reduced and p-mTOR signalling was increased across all arbovirus-exposed placentae, while MMP9 expression was unchanged. Principal components analysis (PCA) distinguished infected from uninfected groups based on placental functional markers related to fetal brain development, but not on histomorphometry. Arboviral-infected placentae showed distinct structural remodelling and altered transporter expression, potentially increasing fetal brain vulnerability and long-term neurodevelopmental risks, even in the absence of neonatal symptoms. KEY POINTS: Virus-specific placental histomorphometric changes were detected, including altered syncytiotrophoblast/syncytial knot, connective tissue and fetal blood vessel areas. Arboviruses reduced the placental efflux transporters P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) and disrupted the expression of ABCA1, SNAT2, GLUT1 and SNAT4 nutrient transporters, while ZIKV additionally reduced SNAT1 expression. Placental functional adaptation to arboviral infection comprised changes in the expression of placental markers of proliferation (Ki-67), angiogenesis (VEGFB), and nutrient sensing (p-mTOR). Arbovirus-exposed placentae exhibited greater functional alterations rather than overt structural pathology, suggesting potential subclinical effects on fetal neurodevelopment, even in the absence of major neonatal abnormalities.
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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 | 0.000 |
| 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".