Gene Expression in Endocrine Tissues
(T476) EXPRESSION PROFILES OF ENDOMETRIA FROM WOMEN WITH NATURAL, MODERATE AND HYPERSTIMULATED CYCLE DURING IN VITRO FERTILIZATION TREATMENT.
Liu, Yunao1, Lee, Kai-Fai1, Ng, Ernest 1, Ho, Pak-Chung1, 1 The University of Hong Kong, Hong Kong, China
ABSTRACT- Objectives: To determine the expression profiles of endometria for three types of women with natural cycles, stimulated in vitrofertilization (IVF) treatment cycles with moderate ovarian response and with excessive ovarian response, and to identify candidate genes as markers for hyper-stimulation cycle. Design: Retrospective, controlled study, Affymetrix GeneChipTM analysis, Real-time PCR analysis. Setting: University infertility clinic and laboratory. Methods: Endometrial biopsies from patients with serum estradiol concentration on the day of hCG>20,000pmol/L (excessive responder, n=17), ≤ 20,000pmol/L (moderate responder, n=15), and natural cycle (n=15) were collected for total RNA isolation. The endometrial mRNA expression profiles of 5 natural-cycles, 4 moderate-responders and 5 excessive-responders were studied using Affymetrix U133A array and further analyzed by Cluster and TreeView programs (http://rana.lbl.gov/EisenSoftware.htm). Results: About 50% (ca. 11,000) of the genes were detected by the Affymetrix array. Cluster analysis demonstrated there were 1241 differentially expressed genes with a 2-fold changes in 6 out of the 14 samples studied. 20 differentially expressed genes with the criteria of high fold-change value (>5-folds) and statistically significant difference (p<0.05) were selected for real-time PCR analysis in all 47 patients. Genes such as glycodelin, stanniocalin, IGF2, GPx3, nicotinamide N-methyltransferase (NNMT) and heparanase were highly expressed (>10-folds); while heparanase 2, and DKK2 were down-regulated (>4-folds) in all hyper-stimulated samples when compared with natural cycle. Similar expression patterns were found in all moderate responders when compared with the natural cycles. Interestingly, no significant difference in the expression levels for the 20 selected genes between the moderate and excessive responders. The mechanisms underlying differential gene expression await further investigation. Conclusions: The present study identified known and new candidate markers that may unveil the underlying mechanisms on endometrial response and receptivity. Acknowledgement: This project is partially supported by a CRCG grant nos. 10205026 and 10205918 to KFL.
KEY WORDS: Endometrium, Microarray, Hyperstimulation, Q-PCR