HOXA11 silencing and endogenous HOXA11 antisense ribonucleic acid in the uterine endometrium

Hoxa11 is an essential regulator of embryonic uterine development and the cyclic development of the adult uterine endometrium. Hoxa11 is required for female fertility, as evidenced by targeted mutation. Here we demonstrate a naturally occurring Hoxa11 (mouse)/HOXA11 (human) antisense transcript present in the adult mouse and human endometrium. HOXA11 antisense transcript levels varied during the menstrual cycle, with peak antisense RNA levels occurring in the midproliferative phase, varying inversely with mRNA expression levels. HOXA11 protein levels correlated temporally with peak mRNA levels. In primary stromal cell culture, progesterone down-regulated HOXA11 antisense transcription, and this was followed by up-regulation of HOXA11 mRNA, suggesting a possible role for the antisense transcript in regulating mRNA expression. Attempts to block Hoxa11 function by transfection of the murine uterus with Hoxa11 antisense oligonucleotides failed to interrupt normal uterine function, suggesting that Hoxa11 antisense does not regulate Hoxa11 mRNA by formulation of sense/antisense duplexes. We propose that HOXA11 antisense functions by transcriptional interference, repressing HOXA11 expression by competing for transcription of the common gene, rather than by sense/antisense interaction.