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

<div><p>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 E₂ receptors and circulating and intra luteal E₂ post PGF_2α treatment. Mining of microarray data revealed several differentially expressed E₂ 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 E₂ responsive genes between both the species. Taken together, the results of this study suggest that PGF_2α interferes with luteotrophic signaling, impairs intra-luteal E₂ levels and regulates various signaling pathways before the effects on structural luteolysis are manifest.</p>