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Title: Early transcriptome responses of the bovine midcycle corpus luteum to prostaglandin F2a includes cytokine signaling

item TALBOTT, HEATHER - Nebraska Medical Center
item HOU, XIAOYING - Nebraska Medical Center
item QIU, FANG - Nebraska Medical Center
item ZHANG, PAN - Nebraska Medical Center
item GUDA, CHITTIBABU - Nebraska Medical Center
item YU, FANG - Nebraska Medical Center
item Cushman, Robert - Bob
item WOOD, JENNIFER - University Of Nebraska
item WANG, CHENG - Nebraska Medical Center
item CUPP, ANDREA - University Of Nebraska
item DAVIS, JOHN - Nebraska Medical Center

Submitted to: Molecular and Cellular Endocrinology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/18/2017
Publication Date: 6/8/2017
Publication URL:
Citation: Talbott, H., Hou, X., Qiu, F., Zhang, P., Guda, C., Yu, F., Cushman, R.A., Wood, J.R., Wang, C., Cupp, A.S., Davis, J.S. 2017. Early transcriptome responses of the bovine midcycle corpus luteum to prostaglandin F2a includes cytokine signaling. Molecular and Cellular Endocrinology. 452:93-109. doi:10.1016/j.mce.2017.05.018.

Interpretive Summary: The ability to control regression of the corpus luteum is an important component in protocols to synchronize estrus for artificial insemination. Synchronization of estrus increases efficiency of artificial insemination because detection of estrus is easier when large groups of cows express behavioral estrus at the same time and labor can be concentrated into a shorter breeding season. Improper response to the hormone that causes regression of the CL, prostaglandin F2alpha (PGF2alpha), can cause inefficiencies in synchronization of estrus. This study examined the pathways activated in the bovine corpus luteum immediately after administration of PGF2alpha to cross-bred beef cows. Global transcript profiling was applied to identify the normal cascade of physiological events that occur in response to a luteolytic dose of PGF2alpha. The abundance of transcription factors was increased very rapidly after administration of PGF2alpha. This was followed by an increase in transcripts for cytokines and genes involved in activation of immune cells. When properly activated these waves of transcriptional activity likely cause an increase in intra-luteal PGF2alpha and inflammatory cytokines that eventually surpass the threshold necessary to drive regression of the CL to completion. Understanding why these mechanisms fail in some cows, will improve the efficiency of synchronization of estrus and increase the use of artificial insemination in the beef industry. Increased use of artificial insemination will allow more rapid genetic advancement through the propagation of sires of superior genetic merit.

Technical Abstract: In ruminants, prostaglandin F2alpha (PGF2a)-mediated luteolysis is essential prior to estrous cycle resumption, and is a target for improving fertility. To deduce early PGF2a-provoked changes in the corpus luteum a short time-course (0.5–4 h) was performed on cows at midcycle. A microarray-determined transcriptome was established and examined by bioinformatic pathway analysis. Classic PGF2a effects were evident by changes in early response genes (FOS, JUN, ATF3) and prediction of active pathways(PKC, MAPK). Several cytokine transcripts were elevated and NF-kappaB and STAT activation were predicted by pathway analysis. Self-organizing map analysis grouped differentially expressed transcripts into ten mRNA expression patterns indicative of temporal signaling cascades. Comparison with two analogous datasets revealed a conserved group of 124 transcripts similarly altered by PGF2a treatment, which both, directly and indirectly, indicated cytokine activation. Elevated levels of cytokine transcripts after PGF2a and predicted activation of cytokine pathways implicate inflammatory reactions early in PGF2a-mediated luteolysis.