The endometrium undergoes cyclic developmental changes and an ordered process of differentiation in response to circulating sex steroids leading to receptivity to implantation. The molecular mechanisms that regulate the ordered proliferation, differentiation, and apoptosis during the normal menstrual cycle are poorly characterized. HOX genes are likely to have a role in the cyclic development of the endometrium in a way similar to that by which they direct embryonic development and the development of the reproductive tract. HOX A genes have been identified in the developing Mullerian system, and their expression persists in the adult female reproductive tract.
In development, both Hoxc10 and Hoxcll are prominently expressed in the posterior urogenital sinus. Later, high levels of expression can be detected in paramesonephric duct and in the genital tubercle. The HOXDIO gene has been shown to be expressed in the human uterus, and Hoxdll transcripts are expressed more anteriorly in the developing Mullerian tract. Although HOXAIO and HOXA11 clearly have a role in cyclic functional human endometrial development resulting in embryonic receptivity, the role of their paralogs has not been defined.