Targeted disruption of both Hoxd9 and Hoxd10 does not alter fertility in female mice and does not result in abnormalities on uterine structure or position. The HOXD10 gene has been shown to be expressed in the human uterus. The expression of HOXD10 in tumors of the uterus, but not ovary or cervix, suggests that it too may also play a role in specifying human uterine identity. Hoxd11 is expressed anteriorly from Hoxa11 or Hoxc11. No genito-urinary abnormality could be detected in Hoxd11 (-/-) female mice; loss-of-function females were fertile.
The Hoxa11/Hoxd11/Hoxc11 triple mutant female mice are infertile and show many of the reproductive defects previously reported in Hoxa11 mutant mice. Overlapping expression and redundant function among paralogous genes likely account for normal development when HOXC and HOXD genes are disrupted by homologous recombination.
The endometrium undergoes an ordered process of differentiation leading to receptivity to implantation. Coordinated expression of multiple HOX genes likely directs this development analogous to the way in which they direct embryonic development. The expression and regulation of HOXC10, HOXC11, HOXD10, and HOXD11, which are paralogs of HOXA10 and HOXA11, are not well characterized in the endometrium. Here, we investigated the expression and regulation of these genes in adult functional endometrial development.