Hoxa-10 regulates uterine stromal cell responsiveness to progesterone during implantation and decidualization in the mouse.

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 PGE2 receptor subtypes, EP3 and EP4, are aberrantly expressed in the uterine stroma in Hoxa-10(−/−) 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 (P4) in the absence of Hoxa-10, while PR, Hoxa-11 and c-myc, three other P4-responsive genes...