Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model

Serena Banu Gumusoglu, Akanksha Sri Satya Chilukuri, Benjamin Wen Qing Hing, Sabrina Marie Scroggins, Sreelekha Kundu, Jeremy Anton Sandgren, Mark Kharim Santillan, Donna Ann Santillan, Justin Lewis Grobe, Hanna Elizabeth Stevens

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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

Original languageEnglish (US)
Article number79
JournalTranslational psychiatry
Volume11
Issue number1
DOIs
StatePublished - Jun 2021
Externally publishedYes

Bibliographical note

Funding Information:
The authors wish to acknowledge the University of Iowa Genomics Core and the Stevens, Santillan, and Grobe labs for helpful discussion. The authors would also like to thank sources of funding support, including the University of Iowa Hypertension grant program, the Iowa Center for Research by Undergraduates, the National Institute of Neurological Disorders and Stroke (Predoctoral Training Grant T32-NS007421 to SBG), and the Roy J. Carver Charitable Trust (to H.E.S., J.L.G., and M.K.S.). This work was also supported by the NIH (HD089940, HD000849, and RR024980 to M.K.S.; HL084207 and HL134850 to J.L.G.; 3UL1TR002537 to M.K.S. and D.A.S.; 3UL1TR 002537-03W1 K Diversity Award NCATS to S.M.S.), March of Dimes (#4-FY18-851 to M.K.S.), and the American Heart Association (AHA) (18SCG34350001 and 19IPLOI34760288 to M.K.S.; 18EIA33890055 to J.L.G.; 19IPLOI34760288 AHA Innovative Project Award and 16POST30960016 AHA Postdoctoral Fellowship to S.M.S.).

Publisher Copyright:
© 2021, The Author(s).

Fingerprint

Dive into the research topics of 'Altered offspring neurodevelopment in an arginine vasopressin preeclampsia model'. Together they form a unique fingerprint.

Cite this