HoxA10 and HoxA11 Regulate the Expression of Contraction-Associated Proteins and Contribute to Regionalized Myometrium Phenotypes in Women.

A relaxed fundus (FUN) and a contracted lower uterine segment (LUS) of human myometrium are required for maintaining pregnancy. How this regional myometrium function is regulated remains unclear. We have previously reported that the homeobox protein A13 (HoxA13) is highly expressed in the LUS and can enhance the expression of contraction-associated proteins (CAPs). Here, we show that in contrast to HoxA13, HoxA10 and HoxA11 genes are expressed at significantly higher levels in myometrium tissues and primary myocytes from the FUN. When introduced exogenously into a human myometrial cell line, HoxA10 and HoxA11 suppress the messenger RNA (mRNA) levels of several CAP genes including interleukin-1 beta (IL-1β), IL-6, connexin 43 (Cx43), and cyclooxygenase 2 (Cox2). Consistently, enhanced HoxA10 and HoxA11 expressions strongly inhibited IL-1β and Cx43 protein levels. We further confirmed that higher expression of HoxA10 and HoxA11 genes in primary myocytes from the FUN compared to that from the LUS was associated with lower expression of IL-1β, IL-6, Cox2, and Cx43 genes. We conclude that the expression patterns of HoxA10, HoxA11, and HoxA13 and their actions in regulating CAP genes in FUN and LUS create regionalized myometrium phenotypes in women that may be important to control regionalized myometrium contractility for maintaining pregnancy.