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Hum. Reprod. Advance Access originally published online on February 6, 2009
Human Reproduction 2009 24(5):1126-1132; doi:10.1093/humrep/dep015
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© The Author 2009. 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

DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and estrogen

Yoshiaki Yamagata, Hiromi Asada, Isao Tamura, Lifa Lee, Ryo Maekawa, Ken Taniguchi, Toshiaki Taketani, Aki Matsuoka, Hiroshi Tamura and Norihiro Sugino1

Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan

1 Correspondence address. Tel: +81-836-22-2286; Fax: +81 836-22-2287; E-mail: sugino{at}yamaguchi-u.ac.jp

BACKGROUND: Epigenetic regulation may be involved in modulation of gene expression during the normal cyclic changes of the human endometrium. We investigated expression of DNA methyltransferases (DNMTs) in endometrium during the menstrual cycle and the influence of sex steroid hormones on DNMT in endometrial stromal cells (ESC) in culture.

METHODS: Expression of DNMT1, DNMT3a and DNMT3b was assessed by immunohistochemistry and real-time RT–PCR in endometrial tissue (n = 42 women). ESC (n = 3 women) were cultured with estradiol and medroxyprogesterone acetate (E + MPA) for 17 days, and DNMT mRNA levels were measured by real-time RT–PCR.

RESULTS: Nuclei of both epithelial and stromal cells immunostained for DNMT1, DNMT3a and DNMT3b during each phase of the menstrual cycle. Tissue levels of DNMT1 and DNMT3a mRNA were significantly lower in the mid-secretory phase than in the proliferative phase (P < 0.01). For DNMT3b, the change in mRNA levels showed a similar trend to that for DNMT3a. In ESC culture, DNMT3a and DNMT3b mRNA levels were significantly decreased by E + MPA treatment (P < 0.01 and P < 0.05, respectively) at Day 8 and Day 17.

CONCLUSIONS: DNMT mRNAs declined in the human endometrium during the secretory phase, and E + MPA down-regulated DNMT3a and DNMT3b mRNAs in ESC in culture. These results suggest that DNMTs have regulatory functions in gene expression that is associated with decidualization.

Key words: DNA methyltransferase/endometrium/endometrial stromal cell/decidualization

Submitted on September 3, 2008; resubmitted on November 18, 2008; accepted on January 13, 2009.


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