This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Horcajadas, J. A. Articles by Simón, C. Search for Related Content PubMed PubMed Citation Articles by Horcajadas, J. A. Articles by Simón, C. Related Collections Female Endocrinology

Effect of an Intrauterine Device on the Gene Expression Profile of the Endometrium

Fundación IVI (J.A.H., F.D., A.P., C.S.), Instituto Universitario IVI, University of Valencia, 46022 Valencia, Spain; Department of Pathology (A.M.S., R.D.C., J.R.A.S.), Reproductive Molecular Research Group, University of Cambridge, Cambridge CB2 1TN, United Kingdom; and Génesis Unidad de Fertilidad y Reproducción (L.A.B., A.C., M.R.P.), Instituto Médico La Floresta, Policlínica Metropolitana, 1060 Caracas, Venezuela

Address all correspondence and requests for reprints to: C. Simón, Fundación IVI, Instituto Universitario IVI, University of Valencia, Valencia, Spain. E-mail: csimon{at}ivi.es.

Context: The human endometrium acquires the ability to allow embryo attachment just for a specific period of time during each menstrual cycle. Understanding of the opposite functional status, referred to as refractoriness, can potentially be used to improve receptivity in infertile patients or as an interceptive approach to prevent gestation.

Objective: The objective of the study was to analyze the endometrial gene expression profile induced by an inert intrauterine device (IUD) at the time of implantation.

Design: We used a microarray containing more than 16,000 cDNAs to investigate the gene expression profile of receptive vs. refractory endometrium in the same women induced by the presence of an IUD. We compared the gene expression profile of endometrium obtained at LH+7 (window of receptivity) from the same women (n = 5) at the following time points: month 1, corresponding to the natural cycle before IUD insertion; month 3, just before IUD removal; and months 5 and 15. Data were validated by quantitative RT-PCR for IGF binding protein-3, peroxisome proliferative activated receptor-, glycodelin, and leukemia inhibitory factor and immunohistochemistry for glycodelin.

Results: We identified 147 genes significantly dysregulated in the refractory endometrium (78 up- and 69 down-regulated). Interestingly, 52 of these genes have previously been reported to be regulated during window of implantation. Surprisingly, the majority of genes (96.6%) remained dysregulated 2 months after IUD removal, but 1 yr later most of them (80%) returned to normal.

Conclusions: Our results reveal that a refractory endometrium in a fertile woman produced by an IUD is induced by preventing the normal transition to a receptive gene expression profile through effects on a specific subset or cluster of genes that impact on endometrial receptivity.

This article has been cited by other articles:

				The ESHRE Capri Workshop Group Intrauterine devices and intrauterine systems Hum. Reprod. Update, May 1, 2008; 14(3): 197 - 208. [Abstract] [Full Text] [PDF]

				A. Tapia, L. M. Gangi, F. Zegers-Hochschild, J. Balmaceda, R. Pommer, L. Trejo, I. M. Pacheco, A. M. Salvatierra, S. Henriquez, M. Quezada, et al. Differences in the endometrial transcript profile during the receptive period between women who were refractory to implantation and those who achieved pregnancy Hum. Reprod., February 1, 2008; 23(2): 340 - 351. [Abstract] [Full Text] [PDF]

				R.D. Catalano, H.O. Critchley, O. Heikinheimo, D.T. Baird, D. Hapangama, J.R.A. Sherwin, D.S. Charnock-Jones, S.K. Smith, and A.M. Sharkey Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium Mol. Hum. Reprod., September 1, 2007; 13(9): 641 - 654. [Abstract] [Full Text] [PDF]