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Title: The plasminogen activator system in the ovine placentome during late gestation and stage-two of parturition

item McNeel, Anthony
item Cushman, Robert - Bob
item Vallet, Jeff

Submitted to: Molecular Reproduction and Development
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/9/2013
Publication Date: 6/1/2013
Publication URL:
Citation: McNeel, A.K., Cushman, R.A., Vallet, J.L. 2013. The plasminogen activator system in the ovine placentome during late gestation and stage-two of parturition. Molecular Reproduction and Development. 80(6):466-473.

Interpretive Summary: Retained placenta is an expensive reproductive disorder for the US dairy industry and occurs when the placenta is not expelled in a timely manner following birth of the calf. In 2010, this disorder accounted for more than 160 million dollars in lost milk production. Retained placenta occurs in beef heifers and in beef cows that are induced to give birth, experience calving difficulty, or produce twins. The mechanisms responsible for expulsion of the placenta during labor are not well understood, but protein degradation appears to play a role in separation of the placenta from the uterus. In this experiment, we used sheep as a model species to investigate the regulation of proteins that are known to play a role in protein degradation. Placental and uterine tissues were collected at specific times during pregnancy and during natural and induced labor. The results indicate that the genes for these proteins were activated between late pregnancy and labor in sheep; however, there was no evidence that the proteins themselves were present or causing degradation. Further work is needed to establish the role that these proteins play in placental separation.

Technical Abstract: The process of placental separation is not completely understood. In domestic animals, especially cattle, it is important that expulsion of the fetal membranes takes place in a timely manner in order to achieve maximal reproductive efficiency. The activity of the matrix-metalloprotease (MMP) family of proteases is known to be reduced in placentomes from cases of retained placenta. Members of the MMP family are known to be activated by the plasminogen activator (PA) family of proteases. We hypothesized that the expression and activity of the PA family increase in the cotyledon and/or caruncle as parturition approaches, with maximal expression and activity at parturition. To test this hypothesis, we performed reverse-transcriptase quantitative PCR and plasminogen-casein zymography to detect the presence and activity of PA familymembers in the placentome leading up to and during parturition in spontaneous and dexamethasone-induced parturient ewes. The results from our experiments indicated that serine proteases inhibitor E1 (SERPINE1) mRNA abundance in the cotyledon was different between treatment groups (P = 0.0002). In the caruncle, gene expression for plasminogen activator urokinase-type (PLAU) was different (P = 0.0154), and there was a strong trend for differences in SERPINE1 expression (P = 0.0565). These results demonstrate that expression of the PA system in the placentome changes from late pregnancy to parturition, and the presence or activity of these enzymes may occur after fetal expulsion.