Analysis of some novel uterine extracellular matrix proteins and a growth factor

This dissertation focused on two classes of molecules implicated in processes of implantation and placentation in sheep and pigs. Study one examined the temporal/spatial distribution of several Small Integrin-Binding Ligand, N-Linked Glycoprotein (SIBLING) family members in cyclic and pregnant ovine uterus. Studies two and three evaluated the relationships between progesterone (P4) and estrogen (E2) and their receptors (PGR and ESR1, respectively) on FGF7 mRNA expression within the endometrium and placenta of pigs. Study one showed that dentin sialophosphoprotein (DSPP) was first detected in luminal epithelium (LE) of Day 15 cyclic and pregnant sheep. Stromal expression of DSPP was first detected on Day 20 of pregnancy in stratum compactum and remained prominent in stroma through Day 120. Stromal DSPP protein was positively influenced by the conceptus based upon analysis of a unilaterally pregnant ewe model system. Immunoreactive dentin matrix protein 1 (DMP1), matrix extracellular phospoglycoprotein (MEPE) were localized to the stroma of cyclic and pregnant sheep, however, these proteins appeared to be constitutively expressed. BSP was not detected in ovine endometrium. Study two determined the effects of E2, P4, P4+E2, P4+the PGR antagonist (ZK137, 316), and P4+E2+ZK on FGF7 mRNA expression in uterine LE of ovariectomized pigs. Results indicate that P4 is permissive to FGF7 mRNA expression by down-regulating PGR in LE; P4 stimulates PGR-positive uterine stromal cells to release an as yet unidentified progestamedin that induces FGF7 mRNA expression by LE; E2 and P4 can induce FGF7 mRNA in the absence of PGR rendered nonfunctional by ZK. Study three showed the expression of ESR1, PGR and FGF7 in the uterine and placental tissue of pregnant pigs from Day 20 through 85. Results reveal a positive correlation between stromal cell expression of PGR and FGF7 mRNA which suggests that P4 is permissive to FGF7 mRNA expression by down-regulating PGR in LE. FGF7 mRNA in later pregnancy is maintained by the release of progestamedin from PGR-positive stromal cells. A novel finding was the presence of ESR1 in porcine placenta on Days 20 through Day 85 of pregnancy suggesting that E2 may play important roles in the placental biology of the pig.