Microarray assessment of the influence of the conceptus on gene expression in the mouse uterus during decidualization

Abstract

During pregnancy in several species including humans and rodents the endometrium undergoes decidualization. This process of differentiation from endometrial to decidual tissue occurs only after the onset of implantation in mice. It can also be artificially-induced causing the formation of deciduomal tissue. The purpose of this study was to compare the gene expression profile of the developing decidua in pregnant mice with the deciduoma formed after artificial induction in an effort to identify conceptus-influenced changes in uterine gene expression during decidualization. We induced decidualization artificially by transferring blastocyst-sized ConA-coated agarose beads into the uterus on Day 2.5 of pseudopregnancy. Recently published work has found this model to be more “physiological” than other methods. Total RNA was isolated from blastocyst and bead induced “implantation” sites of the uteri of Day 7.5 pregnant (decidua) and pseudopregnant (deciduoma) mice, respectively. This RNA was then used for microarray analysis using Mouse Illumina Beadarray chips. This analysis revealed potential differential mRNA levels of only 45 genes between the decidua and bead-induced deciduoma tissues. We confirmed the differential mRNA levels of 31 of these genes using quantitative RT-PCR. Finally, the level and localization of some of the mRNA’s for select genes (Aldh3a1, Bcmo1, Guca2b, and Inhbb) identified by our microarray analysis were examined in more detail. This study provides the identity of a small set of genes whose expression in the uterus during decidualization may be influenced by molecular signals from the conceptus.

Analysis of uterine gene expression in interleukin-15 knockout mice reveals uterine natural killer cells do not play a major role in decidualization and associated angiogenesis

“…5A). Previously, we found uNK cell numbers are significantly decreased in uteri undergoing bead-induced decidualization by days 7.5 and 8.5 (Herington & Bany 2007b) but in a recent microarray study, differences in Avil mRNA levels were not seen between the decidua and deciduoma on Day 7.5 (McConaha et al 2011). Therefore, we examined Avil mRNA levels in IS tissue of pregnant mice and bead-induced deciduomas (BID) of pseudopregnant mice on days 4.5–8.5.…”

“…The expression of several genes such as Vegfa (Halder et al 2000), Ptgs2 (Lim et al 1997, Matsumoto et al 2002), Gja1 (Laws et al 2008), Angpt2 (Matsumoto et al 2002, Hess et al 2006), Tie2 (Matsumoto et al 2002), Flt1, Kdr (Chakraborty et al 1995, Douglas et al 2009) are believed to play a role in angiogenesis in the endometrium during decidualization. Further, several endothelial vascular endothelial cell markers such as Flt4 (Douglas et al 2009), Cd34 (Morison et al 2007), Pecam1 (Ma et al 1997), Adamts9 (Jungers et al 2005) and Inhbb (McConaha et al 2011) have been shown to be expressed in the endometrial endothelial cells during decidualization. Notably, with the exception of Adamts9 which is an anti-angiogenic factor, none of the other genes were differentially expressed in IS tissues between Il15 +/+ and Il15 −/− mice.…”

Limited Colonization Undermined by Inadequate Early Immune Responses Defines the Dynamics of Decidual Listeriosis

“…Artificial deciduomas are masses of decidual tissue that form when an artificial stimulus, such as needle scratching or oil, is applied to the endometrium in a hormonally primed female (30). Importantly, deciduomas display biochemical, architectural, and immunological properties similar to those of true deciduas induced by the implantation of blastocysts (31,32). We used a common approach to generate deciduomas, namely, mating female mice with vasectomized males, followed 3 days later (day 3.5 postcopulation [DPC3.5]) by intrauterine injection of sesame oil.…”

Physiological and molecular determinants of embryo implantation

“…The disappearance of primary decidual zone which forms a barrier surrounding the embryo and reduced immune cell population in deciduoma further emphasize the importance of embryo-uterus dialogue (Herington and Bany, 2007b; Wang et al, 2004d). Using microarray approaches, the differentially expressed genes responsive to (Bany and Cross, 2006; Herington and Bany, 2007a; Herington and Bany, 2007b, 2009; Herington et al, 2009; Kashiwagi et al, 2007; McConaha et al, 2011)the living embryo versus artificial stimuli further prove the paracrine signals from the embryo regulating the decidua development (Bany and Cross, 2006; Herington and Bany, 2007a; Herington and Bany, 2007b, 2009; Herington et al, 2009; Kashiwagi et al, 2007; McConaha et al, 2011). Collectively, these findings highlight the necessity of embryo-derived signals for normal implantation and decidualization.…”