Characterization of the transcriptional landscape of endogenous retroviruses at the fetal-maternal interface in a mouse model of Autism Spectrum Disorder
Authors:
Chiara Cipriani (1), Antonella Camaioni (2), Anna Maria Tartaglione (3), Martina Giudice (1), Vita Petrone (1), Claudia Matteucci (1), Gemma Calamandrei (3), Paola Sinibaldi-Vallebona (1,4), Laura Ricceri (3), Emanuela Balestrieri (1)
Organisations:
1: Department of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
2: Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Ita
3: Centre for Behavioural Sciences and Mental Health, Istituto Superiore di Sanità, Rome, Italy
4: Institute of Translational Pharmacology, National Research Council, Rome, Italy
Presenting author:
Martina Giudice
Exposition date:
Friday, September 15, 2023
Exposition position:
007/1
Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder resulting from the complex interactions among genetic, environmental, and epigenetic factors. A study conducted on two mouse models of ASD, the inbred BTBR T+tf/J (BTBR) mice, and mice prenatally exposed to valproic acid, showed an altered expression of several endogenous retroviruses (ERVs) and cytokines, in whole embryos, blood and brain samples at different post-natal ages, supporting the involvement of ERVs in the ASD pathophysiology. Recently, in a mouse model of maternal immune activation, a deregulated expression of some ERVs and ERV-related genes was found in the prefrontal cortex (PFC) and hippocampus, with higher expression levels in females than in males in PFC (Cipriani et al, 2018 and 2022). ERVs are relics of ancestral germline infections by exogenous retroviruses, stably integrated into the host cellular DNA, involved in the pathogenesis of many human complex diseases. In this work we studied the expression of several ERVs and pro-inflammatory cytokines in dissected embryos and maternal tissues, in order to identify the specific areas in which early ERV overexpression and immune dysregulation occur. Whole embryos from BTBR mice were explanted at gestational day 10.5, separated from maternal tissues and dissected to obtain: cephalic and non-cephalic embryonic tissues, maternal decidua and extra-embryonic tissues. The expression of several ERV families, pro-inflammatory cytokines and Toll-like receptors, were assessed in all tissues by Real-time PCR. The results demonstrated that some ERVs, pro-inflammatory cytokines and Toll-like receptors were expressed at higher levels in BTBR mice compared to controls (i.e. the inbred C57BL6/J strain), depending of the tissue analysed, with the highest levels in embryonic cephalic tissue and maternal decidua. These preliminary results support the hypothesis that changes in the expression of ERVs and inflammatory cytokines could be related, or at least proceed in parallel, with the acquisition of the ASD phenotype.
