Progesterone Resistance in PCOS Endometrium: A Microarray Analysis in Clomiphene Citrate-Treated and Artificial Menstrual Cycles

被引:169
作者
Savaris, Ricardo F. [7 ]
Groll, Jeremy M. [6 ]
Young, Steven L. [5 ]
DeMayo, Franco J. [4 ]
Jeong, Jae-Wook [3 ,4 ]
Hamilton, Amy E. [2 ]
Giudice, Linda C. [2 ]
Lessey, Bruce A. [1 ]
机构
[1] Greenville Hosp Syst, Univ Med Grp, Dept Obstet & Gynecol, Greenville, SC 29605 USA
[2] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
[3] Michigan State Univ, Coll Human Med, Dept Obstet Gynecol & Reprod Biol, Grand Rapids, MI 49503 USA
[4] Baylor Coll Med, Dept Mol Cellular Biol, Houston, TX 77030 USA
[5] Univ N Carolina, Div Reprod Endocrinol & Infertil, Dept Obstet & Gynecol, Chapel Hill, NC 27599 USA
[6] Wright Patterson Med Ctr, Div Reprod Endocrinol & Infertil 88, Wright Patterson AFB, OH 45433 USA
[7] Univ Fed Rio Grande do Sul, Dept Obstet & Ginecol, Programa Posgrad Cirurgia Ciencias Cirugia, BR-90035903 Porto Alegre, RS, Brazil
基金
美国国家卫生研究院;
关键词
PLATELET-ACTIVATING-FACTOR; DNA TOPOISOMERASE-II; GENE-EXPRESSION; ESTROGEN-RECEPTOR; EMBRYO IMPLANTATION; UTERINE RECEPTIVITY; WOMEN; PROTEIN; CANCER; ALPHA;
D O I
10.1210/jc.2010-2600
中图分类号
R5 [内科学];
学科分类号
100201 [内科学];
摘要
Context: Polycystic ovary syndrome (PCOS), the most common endocrinopathy of reproductive-aged women, is characterized by ovulatory dysfunction and hyperandrogenism. Objective: The aim was to compare gene expression between endometrial samples of normal fertile controls and women with PCOS. Design and Setting: We conducted a case control study at university teaching hospitals. Patients: Normal fertile controls and women with PCOS participated in the study. Interventions: Endometrial samples were obtained from normal fertile controls and from women with PCOS, either induced to ovulate with clomiphene citrate or from a modeled secretory phase using daily administration of progesterone. Main Outcome Measure: Total RNA was isolated from samples and processed for array hybridization with Affymetrix HG U133 Plus 2 arrays. Data were analyzed using GeneSpring GX11 and Ingenuity Pathways Analysis. Selected gene expression differences were validated using RT-PCR and/or immunohistochemistry in separately obtained PCOS and normal endometrium. Results: ANOVA analysis revealed 5160 significantly different genes among the three conditions. Of these, 466 were differentially regulated between fertile controls and PCOS. Progesterone-regulated genes, including mitogen-inducible gene 6 (MIG6), leukemia inhibitory factor (LIF), GRB2-associated binding protein 1 (GAB1), S100P, and claudin-4 were significantly lower in PCOS endometrium; whereas cell proliferation genes, such as Anillin and cyclin B1, were up-regulated. Conclusions: Differences in gene expression provide evidence of progesterone resistance in mid-secretory PCOS endometrium, independent of clomiphene citrate and corresponding to the observed phenotypes of hyperplasia, cancer, and poor reproductive outcomes in this group of women. (J Clin Endocrinol Metab 96: 1737-1746, 2011)
引用
收藏
页码:1737 / 1746
页数:10
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