DNA methyltransferase expression in the human endometrium: down-regulation by progesterone and estrogen.
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.
Yamagata
Yoshiaki
Y
Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Minamikogushi 1-1-1, Ube 755-8505, Japan.
Asada
Hiromi
H
Tamura
Isao
I
Lee
Lifa
L
Maekawa
Ryo
R
Taniguchi
Ken
K
Taketani
Toshiaki
T
Matsuoka
Aki
A
Tamura
Hiroshi
H
Sugino
Norihiro
N
D000328:Adult; D002478:Cells, Cultured; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics* / Q000378:metabolism; D000090205:DNA Methyltransferase 3A; D015536:Down-Regulation; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D012739:Gonadal Steroid Hormones / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011374:Progesterone / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism; D000097584:DNA Methyltransferase 3B
D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A; D004967:Estrogens; D012739:Gonadal Steroid Hormones; D011374:Progesterone; D012333:RNA, Messenger; D000097584:DNA Methyltransferase 3B; C000717967:DNMT3A protein, human; C000619380:DNMT1 protein, human