Analysis of differential gene regulation in adequate versus inadequate secretory-phase endometrial complementary deoxyribonucleic acid populations from the rhesus monkey.
The ability to create artificial menstrual cycles in the rhesus monkey provides a model for studies on the regulation of genes and gene networks by estradiol or progesterone (P) in the primate endometrium. This model allowed us to create both a normal level of secretory phase P or an inadequate level of secretory phase P, i.e. endometria that cannot support implantation. The objective of our present study focused on PCR analyses of genes for several factors that are believed to be important in the proper maturation of the endometrium. Complementary DNA (cDNA) populations were prepared from endometria harvested on day 13 (peak E level), days 21-23 of an adequate secretory phase (PcDNA) and days 21-23 of an inadequate secretory phase (IcDNA). Although placental protein 14, leukemia inhibitory factor and 17-beta hydroxysteroid dehydrogenase displayed highly upregulated levels in PcDNA (P-activated genes), there was little or no up-regulation in IcDNA. Transforming growth factor-beta 2 and its receptor and insulin growth factor-I and its receptor were up-regulated in PcDNA, whereas little or no expression was observed in IcDNA. Regulators of the cell cycle and transcription, such as retinoblastoma, c-fos, and c-jun genes, were also greatly underexpressed in IcDNA compared with PcDNA. Interestingly, one gene that we studied, keratinocyte growth factor, that was up-regulated by P (peak E levels vs. PcDNA) was more highly expressed in IcDNA. This latter result suggests that low levels of circulating P are sufficient for expression of this gene, whereas high sustained P levels result in an autologous down-regulation. These data show that the regulation of genes that may play pivotal roles in endometrial maturation are differentially expressed in IcDNA vs. PcDNA and may, in part, characterize improper endometrial maturation.
Department of Obstetrics/Gynecology, University of Massachusetts Medical School, Worcester 01655, USA. William.Okulicz@Banyan.ummed.edu
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D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis; D000818:Animals; D002453:Cell Cycle; D017931:DNA Primers; D018076:DNA, Complementary / Q000032:analysis*; D004717:Endometrium / Q000166:cytology* / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D005786:Gene Expression Regulation; D016161:Genes, Retinoblastoma; D016762:Genes, fos; D016758:Genes, jun; D000071816:Glycodelin; D006023:Glycoproteins / Q000096:biosynthesis; D006131:Growth Inhibitors / Q000096:biosynthesis; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000096:biosynthesis; D008253:Macaca mulatta; D008597:Menstrual Cycle; D016133:Polymerase Chain Reaction; D011257:Pregnancy Proteins / Q000096:biosynthesis; D011374:Progesterone / Q000494:pharmacology / Q000502:physiology; D017346:Protein Serine-Threonine Kinases; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000096:biosynthesis; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D015854:Up-Regulation
D017931:DNA Primers; D018076:DNA, Complementary; D000071816:Glycodelin; D006023:Glycoproteins; D006131:Growth Inhibitors; D015850:Interleukin-6; C507837:LIF protein, human; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018125:Receptors, Transforming Growth Factor beta; D016160:Retinoblastoma Protein; D016212:Transforming Growth Factor beta; D011374:Progesterone; D007334:Insulin-Like Growth Factor I; D015067:17-Hydroxysteroid Dehydrogenases; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II