Investigation of the ruminant materno-fetal interface in health and disease

Author

Caroline K. GriffinFollow

Date of Award

8-2025

Degree Type

Dissertation

Degree Name

Doctor of Philosophy

Major

Comparative and Experimental Medicine

Major Professor

Andrea S. Lear

Committee Members

Brian K. Whitlock, Caleb O. Lemley, Sarah E. Moorey

Abstract

Placental function and immune regulation during pregnancy are critical to fetal development and neonatal outcomes. This series of studies explored placental physiology and immune dynamics in pregnant ruminants under both normal and pathological conditions, focusing on vascular perfusion, biomarker exploration, and responses to viral infection.

The first study assessed the relationship between placentome blood perfusion and circulating pregnancy-associated glycoproteins (PAGs) in pregnant Angus heifers. Using transrectal power flow Doppler ultrasonography and serum PAG assays throughout gestation, the study found a positive linear correlation between PAG concentration and placentome blood perfusion, both of which increased as pregnancy advanced. These findings support the use of noninvasive ultrasonography and circulating PAG concentrations to understand placental health and predict neonatal viability.

The second study examined how in-utero exposure to bovine viral diarrhea virus (BVDV) alters immune development in calves. Heifers were inoculated in early (gestational day 75) or late (GD 200) gestation to induce persistent (PI) or transient (TI) fetal infection, respectively. Postnatal cytokine analysis overall did not differ between groups but is suggestive of a possible pattern of decreased pro- and anti-inflammatory cytokines in TIs compared to CON and PI calves at birth and at three months of age. Transcriptomic analysis of cotyledonary placental tissues from TI calves demonstrated down-regulation of key interferon-stimulated genes and immune response pathways, suggesting an overall blunted immune phenotype with potential implications for postnatal disease susceptibility.

The final study explored placental immune modulation in sheep following mid-gestational BVDV infection. Immunofluorescence and transcriptomic profiling of placentome tissue revealed no significant differences between CD8⁺, CD4⁺, FP3⁺ T cells and IBA1⁺ macrophages between infected and control ewes. Transcriptomic profiling of placentome tissue revealed up-regulation of genes USP18 and IFI44L, both involved in the prevention of autoinflammation in response to viral infection. These data suggest the syncytial placenta modulates immune responses to maintain pregnancy and protect fetal development during gestational viral challenge.

Together, these studies highlight the importance of placental vascular integrity, feto-maternal crosstalk, and immunologic adaptation in the maintenance of pregnancy and mitigation of impacts of maternal viral infection on fetal development and neonatal health.

Recommended Citation

Griffin, Caroline K., "Investigation of the ruminant materno-fetal interface in health and disease. " PhD diss., University of Tennessee, 2025.
https://trace.tennessee.edu/utk_graddiss/12713