Regional development of uterine decidualization: molecular signaling by Hoxa-10

Abstract

Uterine decidualization, a key event in implantation, is critically controlled by stromal cell proliferation and differentiation. Although the molecular mechanism that controls this event is not well understood, the general consensus is that the factors derived locally at the site of implantation influence aspects of decidualization. Hoxa-10, a developmentally regulated homeobox transcription factor, is highly expressed in decidualizing stromal cells, and targeted deletion of Hoxa-10 in mice shows severe decidualization defects, primarily due to the reduced stromal cell responsiveness to progesterone (P(4)). While the increased stromal cell proliferation is considered to be an initiator of decidualization, the establishment of a full-grown functional decidua appears to depend on the aspects of regional proliferation and differentiation. In this regard, this article provides an overview of potential signaling mechanisms mediated by Hoxa-10 that can influence a host of genes and cell functions necessary for propagating regional decidual development.

Figure 1

In situ hybridization for the expression of cyclin G1 and cyclin G2 genes in the uteri of wild-type (WT) and Hoxa-10^−/− mice on Day 4 of pseudopregnancy. Representative dark-field photomicrographs of longitudinal uterine sections are shown at 40×. le, luminal epithelium; s, stroma; myo, myometrium.

Figure 2

In situ hybridization of cdk4 and cdk6 during experimentally induced decidualization on d7 of pseudopregnancy in Hoxa-10^−/− mice as compared to wild-type (WT) littermates. M, mesometrial pole; AM, antimesometrial pole. Bars: 100 μm. Note: The region-specific expression of cdk4 or cdk6 in the corresponding mesometrial or antimesometrial location, as indicated by arrows in the wild-type mice, is lost in Hoxa-10^−/− mice.

Figure 3

In situ hybridization of Hgf and Snail2 during experimentally induced decidualization on day 7 (d7) of pseudopregnancy in Hoxa-10 mutants as compared to wild-type (WT) littermates. M, mesometrial pole; AM, antimesometrial pole. Bars: 100 μm.

Figure 4

In situ hybridization of Gdf10 at the embryo implantation sites (IS) and interimplantation regions (IIS) on Day 7 (d7) of pregnancy in Hoxa-10 mutants as compared to wild-type (WT) littermates. M, mesometrial pole; AM, antimesometrial pole; E, embryo; pdz, primary decidual zone; le, luminal epithelium; s, stroma. Bars: 100 μm.

Figure 5

A scheme depicting potential roles of Hoxa-10 in mediating regional development of decidualization.