Virus-specific alterations in placental structure and transporter expression following maternal arbovirus infection

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.