Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model

摘要: Preeclampsia is a severe gestational hypertensive condition linked to child neuropsychiatric disorders, although underlying mechanisms are unclear. We used recently developed, clinically relevant animal model of preeclampsia assess offspring. C57BL/6J mouse dams were chronically infused with arginine vasopressin (AVP) or saline (24 ng/h) throughout pregnancy. Adult offspring behaviorally tested (Y-maze, open field, rotarod, social approach, and elevated plus maze). Offspring brain was assessed histologically by RNA sequencing. Preeclampsia-exposed adult males exhibited increased anxiety-like behavior approach while females impaired procedural learning. AVP-exposed had reduced total neocortical volume. caudate-putamen volume, cell number, decreased excitatory synapse density in hippocampal dentate gyrus (DG), CA1, CA3. At postnatal day 7 (P7), male female both smaller neocortex. P7, also volume relative size. Similar E18 dorsal forebrain, mainly intermediate, subventricular, ventricular zone particularly males. Decreased not accounted for size cerebrovascular vessel diameter changes. cortical RNAseq revealed 49 differentially-expressed genes offspring, over-representing cytoplasmic translation processes. In females, 31 differentially-expressed, collagen-related epithelial regulation pathways. Gene expression changes placenta indicated potential mechanisms. Deficits forebrain development this AVP-based distinctly different implicating neurobiological bases.