Deletion of placental trophoblast Il6ra prevents behavioral abnormalities in MIA offspring. (A–B) Offspring social behavior was assessed by 3 chamber social test. Maternal saline treated offspring display social preference, whereas they spend more time in the mouse chamber over than object chamber. On the contrary, MIA Il6rafl/fl offspring do not have social preference. Deletion of placental IL-6Rα in MIA offspring display social preference (A) Mouse v.s. Object: Student’s two-tailed unpaired t test; Chamber duration: Saline Cre− t10 = 5.505, p = 0.0003, MIA Cre− t10 = 1.503, p = 0.1637, Saline Cre+ t10 = 12.71, p < 0.0001, MIA Cre+ t10 = 6.032, p = 0.0001. (B) Mouse v.s. Object: Student’s two-tailed unpaired t test Cup investigation time: Saline Cre− t10 = 4.195, p = 0.0018, MIA Cre− t10 = 1.081, p = 0.3053, Saline Cre+ t10 = 5.1777, p = 0.0004, MIA Cre+ t10 = 4.957, p = 0.0006. All groups n = 6 litters (22, 22, 19, 25 offspring were used for Saline Cre−; MIA Cre−; Saline Cre+; MIA Cre+, respectively). (C) Stereotypic/repetitive behavior was measured by marble burying test. Increased repetitive marble burying behavior is seen in MIA Il6rafl/fl offspring, but abrogated in MIA Cyp19-Cre+;Il6rafl/fl offspring (MIA: F(1,20) = 0.5537, p = 0.4655; Cre: F(1,8) = 2.156, p = 0.1576; MIAxCre: F(1,8) = 10.55, p = 0.0040; Post hoc- Saline v.s. MIA: Cre− p = 0.0105, Cre+ p = 0.0919; Cre− v.s. Cre+: Saline p = 0.2226, MIA p = 0.0033)(Two-way ANOVA with Fisher’s LSD post-hoc test). All groups n = 6 litters (22, 22, 26, 25 offspring were used for Saline Cre−; MIA Cre−; Saline Cre+; MIA Cre+, respectively). * p < 0.05, ** p < 0.01, *** p < 0.001, **** p < 0.0001 between groups. Data are presented as mean ± SEM. n.s.: not significant.