The impact of ovarian stimulation with recombinant FSH in combination with GnRH antagonist on the endometrial transcriptome in the window of implantation

被引:55
作者
Macklon, Nick S. [1 ]
van der Gaast, Mark H. [2 ]
Hamilton, Amy [3 ]
Fauser, Bart C. J. M. [1 ]
Gludice, Linda C. [3 ]
机构
[1] UMC Utrecht, Dept Reprod Med & Gynaecol, NL-3584 CX Utrecht, Netherlands
[2] Erasmus MC, Dept Obstet & Gynecol, Rotterdam, Netherlands
[3] Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA
关键词
endometrium; gene expression; ovarian stimulation;
D O I
10.1177/1933719107311781
中图分类号
R71 [妇产科学];
学科分类号
100211 ;
摘要
The aim of this prospective paired cohort study is to elucidate the impact Of ovarian stimulation with recombinant-follicle-stimulating hormone in combination with gonadotropin-releasing hormone antagonist on the endometrial transcrimome. Oocyte donors undenvent endometrial biopsy during the implantation window of the nonstimulated cycle and following ovarian stimulation with recombinant follicle-stimulating hormone and gonadotropin-releasing hormone antagonist but no luteal progesterone supplementation (n = 4). Microarray analysis showed 142 genes to be significantly upregulated and 98 significantly downregulated. Significantly upregulated genes included those sequencing for the chemokine ligand CXCL 13, the Dickkopf homolog, steroidcgenic acute regulatory protein, and homeobox C6. Also upregulated were genes inhibited by progesterone, such as insulin-like growth factor binding protein 5. In conclusion, ovarian stimulation with follicle-stimulating hormone and gonadotropin-releasing hormone antagonist dysregulates the expression of many genes involved in cell adhesion, T-cell receptor signaling, and regulation of signal transduction. These data suggest that dysregulation of the endometrial transcriptome in the stimulated cycle is not fully attributable to supraphysiological sex steroid levels at the folliculo-luteal transition.
引用
收藏
页码:357 / 365
页数:9
相关论文
共 28 条
[1]  
Al-Inany H.G., 2006, COCHRANE DB SYST REV, V3, DOI DOI 10.1002/14651858.CD001750.PUB2
[2]   Follicular and luteal phase characteristics following early cessation of gonadotrophin-releasing hormone agonist during ovarian stimulation for in-vitro fertilization [J].
Beckers, NGM ;
Laven, JSE ;
Eijkemans, MJC ;
Fauser, BCJM .
HUMAN REPRODUCTION, 2000, 15 (01) :43-49
[3]   Nonsupplemented luteal phase characteristics after the administration of recombinant human chorionic gonadotropin, recombinant luteinizing hormone, or gonadotropin-releasing hormone (GnRH) agonist to induce final oocyte maturation in in vitro fertilization patients after ovarian stimulation with recombinant follicle-stimulating hormone and GnRH antagonist cotreatment [J].
Beckers, NGM ;
Macklon, NS ;
Eijkemans, MJ ;
Ludwig, M ;
Felberbaum, RE ;
Diedrich, K ;
Bustion, S ;
Loumaye, E ;
Fauser, BCJM .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2003, 88 (09) :4186-4192
[4]   Depletion of CD8+ cells abolishes the pregnancy protective effect of progesterone substitution with dydrogesterone in mice by altering the Th1/Th2 cytokine profile [J].
Blois, SM ;
Joachim, R ;
Kandil, J ;
Margni, R ;
Tometten, M ;
Klapp, BF ;
Arck, PC .
JOURNAL OF IMMUNOLOGY, 2004, 172 (10) :5893-5899
[5]   Determination of the transcript profile of human endometrium [J].
Borthwick, JM ;
Charnock-Jones, DS ;
Tom, BD ;
Hull, ML ;
Teirney, R ;
Phillips, SC ;
Smith, SK .
MOLECULAR HUMAN REPRODUCTION, 2003, 9 (01) :19-33
[6]   Changes in gene expression during the early to mid-luteal (receptive phase) transition in human endometrium detected by high-density microarray screening [J].
Carson, DD ;
Lagow, E ;
Thathiah, A ;
Al-Shami, R ;
Farach-Carson, MC ;
Vernon, M ;
Yuan, LW ;
Fritz, MA ;
Lessey, B .
MOLECULAR HUMAN REPRODUCTION, 2002, 8 (09) :871-879
[7]   Reproductive biology and IVF: ovarian stimulation and endometrial receptivity [J].
Devroey, P ;
Bourgain, C ;
Macklon, NS ;
Fauser, BCJM .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2004, 15 (02) :84-90
[8]   PROTEOLYTIC MODIFICATION OF INSULIN-LIKE GROWTH FACTOR-BINDING PROTEINS - COMPARISON OF CONDITIONED MEDIA FROM HUMAN CELL-LINES, CIRCULATING PROTEASES AND CHARACTERIZED ENZYMES [J].
FROST, VJ ;
MACAULAY, VM ;
WASS, JAH ;
HOLLY, JMP .
JOURNAL OF ENDOCRINOLOGY, 1993, 138 (03) :545-554
[9]  
Giudice LC, 2003, SEMIN REPROD MED, V21, P119
[10]   INSULIN-LIKE GROWTH-FACTOR BINDING-PROTEINS IN HUMAN ENDOMETRIUM - STEROID-DEPENDENT MESSENGER-RIBONUCLEIC-ACID EXPRESSION AND PROTEIN-SYNTHESIS [J].
GIUDICE, LC ;
MILKOWSKI, DA ;
LAMSON, G ;
ROSENFELD, RG ;
IRWIN, JC .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1991, 72 (04) :779-787