The ovine trophoblast Kunitz domain protein-1: Gene structure, evolution and transcriptional regulation

The trophoblast Kunitz domain proteins (TKDPs) represent a recently evolved, placenta-specific multigene family restricted to ruminant ungulates. Each member of this family possesses a carboxyl-terminal "Kunitz" domain of serine peptidase inhibitory activity preceded by one or more amino-terminal "N" domains of related sequences and unknown function. OvTKDP-1, one of the most abundant secretory products of the sheep placenta, possesses an expression pattern remarkably similar to that of interferon-tau (IFN-tau), the major signal for maternal recognition of pregnancy in cattle and sheep. Considering the physiological importance of IFN-tau in the establishment of pregnancy and the fact that both TKDP-1 and IFN-tau messages are up regulated massively and simultaneously at a critical time when many embryos are lost, it appears that this Kunitz protein has some important function. The almost identical temporal and spatial expression patterns of the TKDP-1 and IFN-tau also led us to hypothesize that these two trophoblast-restricted genes are controlled by similar transcriptional mechanisms. The first objective of the research described here was to gain some insights into how the TKDP-1 gene with its typical Kunitz motif and unusual N domain might have originated. The second objective was to determine the transcriptional regulation of the ovTKDP-1 gene and compare it with the regulation of the IFNT gene expression. The final goal of this research was to determine the nature of the evolutionary pressure operating upon this unique placenta-specific, species-restricted gene family.