Regulation of HOXA-10 and its expression in normal and abnormal endometrium.
HOXA-10 is a member of a family of genes that serve as transcription factors during development and have been shown to be important for uterine function. Using immunohistochemistry and RNAse protection assays (RPA), HOXA-10 was shown to be expressed in both epithelial and stromal cells with increased expression during the window of implantation. By in-vitro culture of isolated endometrial epithelium or stroma, HOXA-10, expression was increased after treatment with oestradiol (10(-8) mol/l) with or without progesterone (10(-6) mol/l). In stromal cells, oestradiol and progesterone both appeared to increase HOXA-10 expression and were additive. Relaxin (30 ng/ml) appeared to further increase stromal HOXA-10 expression. HOXA-10 expression during the window of implantation was compared in normal menstrual cycles to endometrium from women with endometriosis and suspected defects in uterine receptivity. Little or no difference was seen in luminal, glandular or endothelial HOXA-10 expression but a significant reduction in stroma HOXA-10 expression was noted in women with endometriosis. In conclusion, HOXA-10 is a hormone-regulated endometrial transcription factor that appears to be responsive to both ovarian steroids and relaxin. The appearance of this nuclear protein during the window of implantation in epithelium and stroma may offer new insight into the regulation of uterine receptivity and assist in the identification of other genes that are critical to the establishment of a successful pregnancy.
Gui
Y
Y
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of North Carolina, Chapel Hill, NC, USA.
Zhang
J
J
Yuan
L
L
Lessey
B A
BA
D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D010064:Embryo Implantation / Q000502:physiology; D004715:Endometriosis / Q000235:genetics / Q000378:metabolism; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008597:Menstrual Cycle / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D011374:Progesterone / Q000494:pharmacology; D012016:Reference Values; D012065:Relaxin / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism
D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D006727:Hormone Antagonists; C092119:Hoxa10 protein, mouse; D000077267:Fulvestrant; D015735:Mifepristone; D011374:Progesterone; D004958:Estradiol; D012065:Relaxin