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Mol. Hum. Reprod. Advance Access originally published online on May 2, 2008
Molecular Human Reproduction 2008 14(6):357-366; doi:10.1093/molehr/gan023
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© The Author 2008. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Global analysis of genes regulated by HOXA10 in decidualization reveals a role in cell proliferation

Z. Lu, J. Hardt and J.J. Kim1

Division of Reproductive Biology Research, Department of Obstetrics and Gynecology, Robert H. Lurie Comprehensive Cancer Center, 303 E. Superior, Room 4-117, Northwestern University, Chicago, IL 60611, USA

1 Correspondence address. Tel: +1-312-503-5377; Fax: +1-312-503-0095; E-mail: j-kim4{at}northwestern.edu

Homeobox (HOX) A10 is essential for fertility as demonstrated in transgenic mice, specifically affecting implantation and decidualization. Its role in human decidualization, however, remains unknown. In this study, we used gene silencing followed by microarray analysis to decipher the role of HOXA10 during decidualization of human endometrial stromal cells (HESCs). HOXA10 was knocked down using siRNA oligonucleotide transfection and cells were treated with estradiol, medroxyprogesterone acetate and dibutyryl cAMP (H + cAMP) to induce decidualization. Genes significantly regulated were identified using the Affymetrix microarray chip. With this method, 2361 transcripts were significantly altered by 1.5-fold or higher (P < 0.05) with H + cAMP treatment only. Of these genes, 258 were significantly up-regulated by HOXA10 knockdown and 236 transcripts were significantly down-regulated by more than 1.5-fold, totaling 494 genes that were regulated by HOXA10 during decidualization. Data analysis using the Ingenuity System revealed that many of the genes regulated by HOXA10 knockdown during H + cAMP treatment were associated with cell cycle. Real-time PCR was used to confirm that HOXA10 knockdown decreased expression of the cell cycle genes CDC2 and CCNB2. In addition, a higher percentage of cells were arrested in the G2/M phase. Next, we observed that cell proliferation as measured by BrdU incorporation was decreased upon HOXA10 knockdown and H + cAMP treatment. Apoptosis, on the other hand, as measured by Annexin V staining was not influenced by siHOXA10 in decidualizing cells. Together, these data demonstrate that during decidualization of HESC, HOXA10 is actively involved in promoting cell proliferation through the regulation of hundreds of genes.

Key words: decidualization/HOXA10/endometrium/gene silencing/microarray analysis

Submitted on January 28, 2008; resubmitted on April 14, 2008; accepted on April 25, 2008.


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