| Description |
Decidualization of endometrial stromal cells is a prerequisite for successful implantation and maintenance of pregnancy in most mammalian species. This process is under the regulation of progesterone, which in turn modulates expression of various factors leading to decidualization. Amongst the various factors regulated by progesterone, HOXA10 has emerged as a potential candidate for induction of decidualization, as mice knockout for hoxa10 show severe impairment in decidualization and failure of implantation. However, the roles of HOXA10 in endometrial decidualization in primate endometrium are unknown.
To gain an insight into the roles of HOXA 10 in adult uterus particularly during implantation, we have examined the expression profiles of HOXA10 in the endometrium of bonnet monkeys (Macaca radiata) in conception and non-conception cycles. We observed that HOXA10 is differentially expressed in the two zones of endometrium and is modulated in vivo by the signals from incoming embryo.
To define the role of HOXA10 in the process of decidualization, we perturbed its endogenous expression by siRNA in decidualized human endometrial stromal cells in vitro. We demonstrated that HOXA10 is required for maintenance of steroid hormone mediated decidualization in vitro. Further, to identify the pathways regulated by HOXA10, global gene profiling was carried out of decidual cells knocked down for HOXA10 by siRNA. The results revealed a large scale change in the decidual cell transcriptome that is temporally controlled in response to HOXA10 knockdown. Analysis of differentially expressed genes identified genes belonging to diverse pathways that are under the regulation of HOXA10. In this study, using combinatorial approaches, we have identified two new HOXA10 dependent pathways in the decidual cells. The presentation will cover in vivo regulation of HOXA10 expression, with the main emphasis on the outcomes of microarray study including the in depth validation of pathways and eventually the functional implication of the findings will be discussed.
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