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In mouse models of maternal immune activation (MIA), different toll\u2010like receptors (TLRs) are stimulated to initiate inflammatory responses in mother and fetus. The goal of this study was to determine sex\u2010dependent aspects of MIA using a TLR7\/8 agonist, Resiquimod (RQ), on neurodevelopment. RQ was administered to timed\u2010pregnant mice on embryonic day (E) 12.5. At E15, maternal\/fetal plasma cytokines were measured by enzyme\u2010linked immunosorbent assay (ELISA). Maternal cytokines interleukin (IL)\u20106 and IL\u201010 were higher while tumor necrosis factor (TNF)\u2010\u03b1 and IL\u201017 were lower in pregnant dams exposed to RQ. Fetal cytokines (E15) were altered at the same timepoint with fetal plasma IL\u20106 and IL\u201017 greater after RQ compared to vehicle, while IL\u201010 and TNF\u2010\u03b1 were higher in male fetuses but not female. Other timed\u2010pregnant dams were allowed to give birth. MIA with RQ did not alter the female to male ratio of offspring born per litter. Body weights were reduced significantly in both sexes at birth, and over the next 5\u2009weeks. Offspring from RQ\u2010injected mothers opened their eyes 5\u2009days later than controls. Similarly, female offspring from RQ\u2010injected mothers exhibited pubertal delay based on vaginal opening 2\u20133\u2009days later than control females. On the behavioral side, juvenile and adult male and female MIA offspring exhibited less social\u2010like behavior in a social interaction test. Anhedonia\u2010like behavior was greater in MIA adult female mice. This study provides support for sex\u2010dependent influences of fetal antecedents for altered brain development and behavioral outputs that could be indicative of increased susceptibility for adult disorders through immune mechanisms. Future studies are needed to determine neural cellular and molecular mechanisms for such programming effects.<\/jats:p>","DOI":"10.1111\/jne.13417","type":"journal-article","created":{"date-parts":[[2024,6,1]],"date-time":"2024-06-01T09:03:20Z","timestamp":1717232600000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Maternal immune activation with toll\u2010like receptor 7 agonist during mid\u2010gestation alters juvenile and adult developmental milestones and behavior"],"prefix":"10.1111","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6192-1060","authenticated-orcid":false,"given":"Julietta A.","family":"Sheng","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences Colorado State University  Fort Collins Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1615-7331","authenticated-orcid":false,"given":"Stuart 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