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Title: Rapid induction of gene expression in the corpus luteum following in vivo treatment with prostaglandin F2 alpha

item DAVIS, JOHN - Nebraska Medical Center
item HOU, XIAOYING - Nebraska Medical Center
item MARONI, DULCE - Nebraska Medical Center
item TALBOTT, HEATHER - Nebraska Medical Center
item FAN, JING - Nebraska Medical Center
item GUDA, CHITTIBABU - Nebraska Medical Center
item YU, FANG - Nebraska Medical Center
item Cushman, Robert - Bob
item CUPP, ANDREA - University Of Nebraska

Submitted to: Biology of Reproduction Abstracts
Publication Type: Abstract Only
Publication Acceptance Date: 3/21/2011
Publication Date: 7/30/2011
Citation: Davis, J.S., Hou, X., Maroni, D., Talbott, H., Fan, J., Guda, C., Yu, F., Cushman, R.A., Cupp, A.S. 2011. Rapid induction of gene expression in the corpus luteum following in vivo treatment with prostaglandin F2 alpha [abstract]. Biology of Reproduction. 85 (1 Supplement):111 (Abstract # 229).

Interpretive Summary:

Technical Abstract: The pulsatile uterine secretion of prostaglandin F2 alpha (PGF) triggers the regression of the corpus luteum (CL). Research from many laboratories has identified the early intracellular signaling events initiated by PGF (for example, activation of phospholipases, increased intracellular calcium, and the activation of protein kinases) and their involvement in the induction of early response genes like FOS, JUN, and early growth response 1 (EGR1). Recent studies have used microarray analysis to examine global patterns of gene expression approximately 24 hours following induction of luteal regression; however, little is currently known about the rapid effects of PGF on gene expression at times corresponding to the early intracellular signaling events initiated by PGF. The present experiments were performed to examine rapid gene expression profiles in luteal tissue following in vivo treatment with PGF. Postpubertal female cattle of composite breeding were treated at midcycle (days 9-10) with saline (n=3) or PGF (Lutalyse, n=3). Ovariectomies were performed after 60 minutes and RNA was isolated from CL. Affymetrix bovine microarrays (23,000 targets; n = 1 chip per cow) were screened for differential gene expression. Statistical analysis revealed that 181 genes were significantly up-regulated (P < 0.05) with fold changes ranging from 1.42 to 50.77; 60 of these genes were not annotated. Ninety-five (95) annotated genes were significantly up-regulated at least 2 fold (range 2-20 fold). Ingenuity Pathway Analysis (IPA, version 8.8) was used for analysis of networks, molecular and cellular functions, and canonical pathways of genes up-regulated at least 2 fold. The most highly differentially expressed gene activating transcription factor 3 (ATF3) encodes a transcriptional repressor. Expression of ATF3 was verified by RT-PCR and Western blot analysis of samples collected following in vivo and in vitro treatment with PGF. Adenoviral-mediated overexpression of ATF3 in luteal cells resulted in a significant reduction (P < 0.05) in progesterone secretion. Microarray analysis PGF-induced expression of the transcription factors [FOS (9.3 fold), JUN (7.9 fold) and EGR1 (3.9 fold)] and chemokines [CCL2 (3.4 fold) and IL8 (6.9 fold)] confirmed previously published reports. Primary biological functions implicated were: apoptosis (59 genes), gene expression (46 genes), tissue morphology (37 genes), inflammatory responses (38 genes), cell-to-cell signaling (32 genes), and connective tissue function (31 genes). Further analysis revealed up-regulated expression of genes involved in leukocyte chemotaxis (CXCL2, IL8, ANGPT2, PLAU, CCL2, and CCL8) and fibrosis (ATF3, PDGFB, EGR1, BMP2, JUN, AREG, PLAT, KLF4), two physiologic responses occurring during luteal regression. Microarray analysis extends knowledge of the early response genes activated in the CL in response to PGF, which entails differential expression of genes encoding transcription factors and chemokines as well as genes altering apoptosis, tissue morphology and fibrosis. USDA AFRI 2011-67015-20076. USDA is an equal opportunity provider and employer.