This Article Full Text Full Text (PDF) Supplemental Data Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Priyanka, S. Articles by Medhamurthy, R. Search for Related Content PubMed PubMed Citation Articles by Priyanka, S. Articles by Medhamurthy, R.

Genome-Wide Gene Expression Analysis Reveals a Dynamic Interplay between Luteotropic and Luteolytic Factors in the Regulation of Corpus Luteum Function in the Bonnet Monkey (Macaca radiata)

Department of Molecular Reproduction, Development and Genetics (S.P., P.J., R.M.) and Primate Research Laboratory (R.M.), Indian Institute of Science, Bangalore 560012, India; and Department of Physiology (R.S.), Morehouse School of Medicine, Atlanta, Georgia 30310-1495

Address all correspondence and requests for reprints to: R. Medhamurthy, Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science, Bangalore 560012, India. E-mail: rmm{at}mrdg.iisc.ernet.in.

Although LH is essential for survival and function of the corpus luteum (CL) in higher primates, luteolysis occurs during nonfertile cycles without a discernible decrease in circulating LH levels. Using genome-wide expression analysis, several experiments were performed to examine the processes of luteolysis and rescue of luteal function in monkeys. Induced luteolysis with GnRH receptor antagonist (Cetrorelix) resulted in differential regulation of 3949 genes, whereas replacement with exogenous LH (Cetrorelix plus LH) led to regulation of 4434 genes (1563 down-regulation and 2871 up-regulation). A model system for prostaglandin (PG) F₂-induced luteolysis in the monkey was standardized and demonstrated that PGF₂ regulated expression of 2290 genes in the CL. Analysis of the LH-regulated luteal transcriptome revealed that 120 genes were regulated in an antagonistic fashion by PGF₂. Based on the microarray data, 25 genes were selected for validation by real-time RT-PCR analysis, and expression of these genes was also examined in the CL throughout the luteal phase and from monkeys treated with human chorionic gonadotropin (hCG) to mimic early pregnancy. The results indicated changes in expression of genes favorable to PGF₂ action during the late to very late luteal phase, and expressions of many of these genes were regulated in an opposite manner by exogenous hCG treatment. Collectively, the findings suggest that curtailment of expression of downstream LH-target genes possibly through PGF₂ action on the CL is among the mechanisms underlying cross talk between the luteotropic and luteolytic signaling pathways that result in the cessation of luteal function, but hCG is likely to abrogate the PGF₂-responsive gene expression changes resulting in luteal rescue crucial for the maintenance of early pregnancy.