SAT-142 Gestational Zika Infection: Endocrine Disruption, Maternal Behavior, and Neonatal Mortality in Mice

Abstract Disclosure: A.C. Valim: None. V.M. Nascimento: None. C.B. Andrade: None. S.V. Coelho: None. L.B. Arruda: None. D. Pereira-Carvalho: None. T.M. Ortiga-Carvalho: None. The Zika virus (ZIKV) is known to cause severe complications in humans, including microcephaly in newborns of mothers infected during pregnancy. ZIKV infection of the placenta can compromise gestational development by affecting hormonal production, which is essential for maintaining pregnancy and maternal behavior postpartum. We investigated the effects of ZIKV infection during pregnancy in mice, focusing on changes in maternal behavior and neonatal survival and offspring development. We investigated the effects of ZIKV infection during pregnancy in mice, focusing on changes in maternal behavior, neonatal survival, and offspring development. Female C57BL/6 mice were infected with ZIKV (ZIKV-BRPE243 strain) on gestational day (GD) 12.5, divided into groups: High Dose ZIKV (ZIKV HD; 5x107 PFU; n=25) and Low Dose ZIKV (ZIKV LD; 103 PFU; n=27) and Control (CTR; noninfected medium; n=31). We assessed offspring survival and development, including behavioral tests. We analyzed the expression of placental genes related to maternal behavior and hormonal production (Phlda2, Prl7a2, Prl8a8, Prl3a1, Prl3b1), as well as serum prolactin levels on GD 18.5. Data were analyzed using One-way ANOVA with Tukey post-hoc test, Mann-Whitney test, Mixed ANOVA with Greenhouse-Geisser correction and Log-rank test. Infection with a high viral load of ZIKV resulted in 100% neonatal mortality (p=0.002). In the ZIKV LD group, 77.2% of females completed the cliff avoidance test, compared to 50% in the CTR group (p=0.038). ZIKV LD-infected mothers built higher-quality nests (p=0.008). No significant changes were observed in the expression of placental genes related to hormonal production or serum prolactin levels on GD 18.5. Our findings suggest that low viral load activates compensatory mechanisms, possibly involving the hypothalamic-pituitary-adrenal (HPA) axis in mothers and female offspring. Conversely, high viral load appears to overwhelm mothers, preventing effective activation of these mechanisms and contributing to elevated mortality. Further investigation of HPA axis components in both mothers and offspring is warranted to validate this hypothesis. These results highlight the importance of understanding the endocrine alterations induced by ZIKV infection during gestation and their implications for maternal behavior and neonatal survival. Keywords: ZIKV; maternal behavior; placenta. Presentation: Saturday, July 12, 2025