| First Author | Lim H | Year | 1999 |
| Journal | Mol Endocrinol | Volume | 13 |
| Issue | 6 | Pages | 1005-17 |
| PubMed ID | 10379898 | Mgi Jnum | J:55408 |
| Mgi Id | MGI:1337917 | Doi | 10.1210/mend.13.6.0284 |
| Citation | Lim H, et al. (1999) Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse. Mol Endocrinol 13(6):1005-17 |
| abstractText | Hoxa-10 is an AbdominalB-like homeobox gene that is expressed in the developing genitourinary tract during embryogenesis and in the adult uterus during early pregnancy. Null mutation of Hoxa-10 in the mouse causes both male and female infertility. Defective implantation and decidualization resulting from the loss of maternal Hoxa-10 function in uterine stromal cells is the cause of female infertility. However, the mechanisms by which Hoxa- 10 regulates these uterine events are unknown. We have identified two potential mechanisms for these uterine defects in Hoxa-10(-/-) mice. First, two PGE(2) receptor subtypes, EP3 and EP4, are aberrantly expressed in the uterine stroma in Hoxa10(-/-) mice, while expression of several other genes in the stroma (TIMP-2, MMP-2, ER, and PR) and epithelium (LIF, HB-EGF, Ar, and COX-1) are unaffected before implantation. Further, EP3 and EP4 are inappropriately regulated by progesterone (P-4) in the absence of Hoxa-10, while PR, Hoxa-11 and c-myc, three other P-4-responsive genes respond normally. These results suggest that Hoxa-10 specifically mediates P-4 regulation of EP3 and EP4 in the uterine stroma. Second, since Hox genes are implicated in local cell proliferation, we also examined steroid-responsive uterine cell proliferation in Hoxa-10(-/-) mice. Stromal cell proliferation in mutant mice in response to P-4 and 17 beta-estradiol (E-2) was significantly reduced, while epithelial cell proliferation was normal in response to E-2. These results suggest that stromal cell responsiveness to P-4 with respect to cell proliferation is impaired in Hoxa-10(-/-) mice, and that Hoxa-10 is involved in mediating stromal cell proliferation. Collectively, these results suggest that Hoxa-10 mutation causes specific stromal cell defects that can lead to implantation and decidualization defects apparently without perturbing epithelial cell functions. |
