Profiling of Luteal Transcriptome during Prostaglandin F2-Alpha Treatment in Buffalo Cows: Analysis of Signaling Pathways Associated with Luteolysis

In several species including the buffalo cow, prostaglandin (PG) F(2α) is the key molecule responsible for regression of corpus luteum (CL). Experiments were carried out to characterize gene expression changes in the CL tissue at various time points after administration of luteolytic dose of PGF(2α) in buffalo cows. Circulating progesterone levels decreased within 1 h of PGF(2α) treatment and evidence of apoptosis was demonstrable at 18 h post treatment. Microarray analysis indicated expression changes in several of immediate early genes and transcription factors within 3 h of treatment. Also, changes in expression of genes associated with cell to cell signaling, cytokine signaling, steroidogenesis, PG synthesis and apoptosis were observed. Analysis of various components of LH/CGR signaling in CL tissues indicated decreased LH/CGR protein expression, pCREB levels and PKA activity post PGF(2α) treatment. The novel finding of this study is the down regulation of CYP19A1 gene expression accompanied by decrease in expression of E(2) receptors and circulating and intra luteal E(2) post PGF(2α) treatment. Mining of microarray data revealed several differentially expressed E(2) responsive genes. Since CYP19A1 gene expression is low in the bovine CL, mining of microarray data of PGF(2α)-treated macaques, the species with high luteal CYP19A1 expression, showed good correlation between differentially expressed E(2) responsive genes between both the species. Taken together, the results of this study suggest that PGF(2α) interferes with luteotrophic signaling, impairs intra-luteal E(2) levels and regulates various signaling pathways before the effects on structural luteolysis are manifest.