Altered structural and transporter-related gene expression patterns in the placenta play a role in fetal demise during Porcine reproductive and respiratory syndrome virus infection

Authors: Van Goor, Angelica; PASTERNAK, J - Purdue University; Walker, Kristen; Chick, Shannon; HARDING, JOHN - University Of Saskatchewan; Lunney, Joan

Submitted to: BMC Genomics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/21/2025
Publication Date: 3/21/2025
Citation: Van Goor, A.G., Pasternak, J.A., Walker, K.E., Chick, S.T., Harding, J.C., Lunney, J.K. 2025. Altered structural and transporter-related gene expression patterns in the placenta play a role in fetal demise during Porcine reproductive and respiratory syndrome virus infection. BMC Genomics. 26. Article e279. https://doi.org/10.1186/s12864-025-11397-0.
DOI: https://doi.org/10.1186/s12864-025-11397-0

Interpretive Summary: Congenital infection of gilts with porcine reproductive and respiratory syndrome virus (PRRSV) in late gestation causes fetal morbidity and mortality. We wanted to verify the cause of this pathology. We tested expression of placental structural and transporter-related genes fetuses at 12 days post maternal infection. We determined that fetal PRRSV infection levels resulted in strongly decreased placental expression of solute transporters as well as structural genes, e.g. integrins and actin cytoskeleton genes, and changes in arachidonic acid and VEGF signaling. These data support the concept that fetal PRRSV infection levels, rather than fetal demise alone, is necessary for transcriptional dysregulation of the fetal placenta, and death of susceptible fetuses.

Technical Abstract: Background Porcine reproductive and respiratory syndrome virus (PRRSV) can be transmitted across the maternal-fetal-interface from an infected gilt to her fetuses. Although fetal infection status and disease outcomes vary, the mechanisms are not completely understood. The objective was to assess targeted placental structural and transporter-related gene expression patterns. At day 85 of gestation pregnant pigs were challenged with PRRSV, and at 12 days post maternal infection sows and fetuses were sacrificed, and the placental tissue was collected. Grouping of fetuses was by preservation status and PRRS viral load (VL): control (CTRL, n'='14), viable and low VL fetus (VIA_LVF, n'='15), viable and high VL fetus (VIA_HVF, n'='21), meconium mild and low VL fetus (MECm_LVF, n'='14), meconium mild and high VL fetus (MECm_HVF, n'='14), and meconium severe and high VL fetus (MECs_HVF, n'='13). NanoString was used to evaluate the expression of 86 genes: actin cytoskeleton signaling, arachidonic acid pathway, integrin signaling, intercellular junctions, transporters, and VEGF signaling. Statistical analyses were performed using Limma with P'='0.05 considered significant. Results We identified 1, 7, 0, 29, and 39 differentially expressed genes in VIA_LVF, VIA_HVF, MECm_LVF, MECm_HVF, and MECs_HVF, respectively, contrasted to CTRL. Placental transporter genes were significantly impacted (i.e., downregulation of SLC1A3, SLC1A5, SLC2A1, SLC2A3, SLC2A5, SLC2A10, SLC2A12, SLC7A4, SLC16A5, SLC16A10, and SLC27A6; and upregulation of SLC2A2, SLC16A3, and SLC27A4), compared to CTRL. Actin cytoskeleton signaling (ARHGEF6 and ARHGEF7), arachidonic acid (PTGES3 and PTGIS), integrin signaling (FN1 and ITGB6), intercellular junctions (CDH3 and CDH11), and VEGF signaling (MAPK3 and HPSE) gene groupings were significantly impacted, compared to CTRL. Conclusion Data reported here indicate that fetal PRRSV infection levels rather than fetal demise is necessary for transcriptional dysregulation of the fetal placenta, with a tendency towards more downregulation in the target gene sets among susceptible fetuses. These results generally support that in susceptible fetuses there is altered solute transportation, placental structural integrity, and reduced angiogenesis. The data described here is associated with fetal PRRS resistance/resilience and susceptibility.