Endocrinology, Vol 137, 4844-4850, Copyright © 1996 by Endocrine Society

ARTICLES

Analysis of differential gene regulation in adequate versus inadequate secretory-phase endometrial complementary deoxyribonucleic acid populations from the rhesus monkey

WC Okulicz, CI Ace, C Longcope and J Tast
Department of Obstetrics/Gynecology, University of Massachusetts Medical School, Worcester 01655, USA. William.Okulicz@Banyan.ummed.edu

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.

This article has been cited by other articles:

				G. C. Rodriguez, B.J. Rimel, W. Watkin, J. M. Turbov, C. Barry, H. Du, G. L. Maxwell, and J.M. Cline Progestin Treatment Induces Apoptosis and Modulates Transforming Growth Factor-{beta} in the Uterine Endometrium Cancer Epidemiol. Biomarkers Prev., March 1, 2008; 17(3): 578 - 584. [Abstract] [Full Text] [PDF]

				R. O. Burney, S. Talbi, A. E. Hamilton, K. C. Vo, M. Nyegaard, C. R. Nezhat, B. A. Lessey, and L. C. Giudice Gene Expression Analysis of Endometrium Reveals Progesterone Resistance and Candidate Susceptibility Genes in Women with Endometriosis Endocrinology, August 1, 2007; 148(8): 3814 - 3826. [Abstract] [Full Text] [PDF]

				Z. A. Radi and N. K. Khan Comparative Expression and Distribution of c-fos, Estrogen Receptor{alpha} (ER{alpha}), and p38{alpha} in the Uterus of Rats, Monkeys, and Humans Toxicol Pathol, June 1, 2006; 34(4): 327 - 335. [Abstract] [Full Text] [PDF]

				W. C. Okulicz and C. I. Ace Temporal Regulation of Gene Expression During the Expected Window of Receptivity in the Rhesus Monkey Endometrium Biol Reprod, November 1, 2003; 69(5): 1593 - 1599. [Abstract] [Full Text] [PDF]

				M. S.T. Torres, C. I. Ace, and W. C. Okulicz Assessment and Application of Laser Microdissection for Analysis of Gene Expression in the Rhesus Monkey Endometrium Biol Reprod, October 1, 2002; 67(4): 1067 - 1072. [Abstract] [Full Text] [PDF]

				R. E. Leach, R. Khalifa, D. R. Armant, A. Brudney, S. K. Das, S. K. Dey, and A. T. Fazleabas Heparin-Binding EGF-Like Growth Factor Modulation by Antiprogestin and CG in the Baboon (Papio anubis) J. Clin. Endocrinol. Metab., September 1, 2001; 86(9): 4520 - 4528. [Abstract] [Full Text] [PDF]

				S.D. Kholkute, R.R. Katkam, T.D. Nandedkar, and C.P. Puri Leukaemia inhibitory factor in the endometrium of the common marmoset Callithrix jacchus: localization, expression and hormonal regulation Mol. Hum. Reprod., April 1, 2000; 6(4): 337 - 343. [Abstract] [Full Text] [PDF]

				C. I. Ace and W. C. Okulicz Identification of Progesterone-Dependent Messenger Ribonucleic Acid Regulatory Patterns in the Rhesus Monkey Endometrium by Differential-Display Reverse Transcription-Polymerase Chain Reaction Biol Reprod, April 1, 1999; 60(4): 1029 - 1035. [Abstract] [Full Text]