Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis

被引:568
作者
Burney, Richard O.
Talbi, Said
Hamilton, Amy E.
Vo, Kim Chi
Nyegaard, Mette
Nezhat, Camran R.
Lessey, Bruce A.
Giudice, Linda C. [1 ]
机构
[1] Stanford Univ, Dept Obstet & Gynecol, Stanford, CA 94305 USA
[2] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
[3] Univ Med Grp, Greenville Hosp Syst, Dept Obstet & Gynecol, Greenville, SC 29605 USA
关键词
D O I
10.1210/en.2006-1692
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The identification of molecular differences in the endometrium of women with endometriosis is an important step toward understanding the pathogenesis of this condition and toward developing novel strategies for the treatment of associated infertility and pain. In this study, we conducted global gene expression analysis of endometrium from women with and without moderate/ severe stage endometriosis and compared the gene expression signatures across various phases of the menstrual cycle. The transcriptome analysis revealed molecular dysregulation of the proliferative-to-secretory transition in endometrium of women with endometriosis. Paralleled gene expression analysis of endometrial specimens obtained during the early secretory phase demonstrated a signature of enhanced cellular survival and persistent expression of genes involved in DNA synthesis and cellular mitosis in the setting of endometriosis. Comparative gene expression analysis of progesterone- regulated genes in secretory phase endometrium confirmed the observation of attenuated progesterone response. Additionally, interesting candidate susceptibility genes were identified that may be associated with this disorder, including FOXO1A, MIG6, and CYP26A1. Collectively these findings provide a framework for further investigations on causality and mechanisms underlying attenuated progesterone response in endometrium of women with endometriosis.
引用
收藏
页码:3814 / 3826
页数:13
相关论文
共 93 条
[71]   Relative expression software tool (REST©) for group-wise comparison and statistical analysis of relative expression results in real-time PCR -: art. no. e36 [J].
Pfaffl, MW ;
Horgan, GW ;
Dempfle, L .
NUCLEIC ACIDS RESEARCH, 2002, 30 (09)
[72]  
Sampson JA., 1927, AM J OBSTET GYNECOL, V14, P442
[73]   CHARACTERIZATION OF THE HORMONE RESPONSIVE ELEMENT INVOLVED IN THE REGULATION OF THE PROGESTERONE-RECEPTOR GENE [J].
SAVOURET, JF ;
BAILLY, A ;
MISRAHI, M ;
RAUCH, C ;
REDEUILH, G ;
CHAUCHEREAU, A ;
MILGROM, E .
EMBO JOURNAL, 1991, 10 (07) :1875-1883
[74]  
SCHENKEN RS, 1980, FERTIL STERIL, V34, P581
[75]   FOXO1 and c-jun transcription factors mRNA are modulated in endometriosis [J].
Shazand, K ;
Baban, S ;
Privé, C ;
Malette, B ;
Croteau, P ;
Lagacé, M ;
Racine, JB ;
Hugo, P .
MOLECULAR HUMAN REPRODUCTION, 2004, 10 (12) :871-877
[76]   Stanniocalcin (STC) in the endometrial glands of the ovine uterus: Regulation by progesterone and placental hormones [J].
Song, G ;
Bazer, FW ;
Wagner, GF ;
Spencer, TE .
BIOLOGY OF REPRODUCTION, 2006, 74 (05) :913-922
[77]  
STEINLEITNER A, 1990, FERTIL STERIL, V53, P926
[78]   Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women [J].
Talbi, S ;
Hamilton, AE ;
Vo, KC ;
Tulac, S ;
Overgaard, MT ;
Dosiou, C ;
Le Shay, N ;
Nezhat, CN ;
Kempson, R ;
Lessey, BA ;
Nayak, NR ;
Giudice, LC .
ENDOCRINOLOGY, 2006, 147 (03) :1097-1121
[79]   HOX gene expression is altered in the endometrium of women with endometriosis [J].
Taylor, HS ;
Bagot, C ;
Kardana, A ;
Olive, D ;
Arici, A .
HUMAN REPRODUCTION, 1999, 14 (05) :1328-1331
[80]   Promegestone (R5020) and mifepristone (RU486) both function as progestational agonists of human glycodelin gene expression in isolated human epithelial cells [J].
Taylor, RN ;
Savouret, JF ;
Vaisse, C ;
Vigne, JL ;
Ryan, I ;
Hornung, D ;
Seppälä, M ;
Milgrom, E .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1998, 83 (11) :4006-4012