Comparative Analysis of Mouse Decidualization Models at the Molecular Level

Abstract

The mouse is widely used to study decidualization and there are three well-established mouse models of decidualization, namely natural pregnancy decidualization (NPD), artificial decidualization (AD), and in vitro decidualization (IVD). However, the extent of similarity and difference between these models at the molecular level remains largely unknown. Here, we performed a comparative analysis using the RNA-seq approach. In the NPD model, which is thought to be the golden standard of mouse decidualization, we found a total of 5277 differentially expressed genes, with 3158 genes being up-regulated and 2119 genes being down-regulated. A total of 4294 differentially expressed genes were identified in the AD model: 1127 up-regulated genes and 3167 down-regulated genes. In comparison to NPD, 1977 genes were consistently expressed, whereas only 217 genes were inconsistently expressed, indicating that AD is a reliable model for mouse decidualization. In the IVD model, RNA-seq analysis revealed that 513 genes were up-regulated and 988 genes were down-regulated. Compared to NPD, 310 genes were consistently expressed, whereas 456 genes were inconsistently expressed. Moreover, although the decidualization marker Prl8a2 (prolactin family 8 subfamily a member 2) was up-regulated, the widely-used marker Alpl (alkaline phosphatase liver/bone/kidney) was down-regulated in the IVD model. Therefore, we suggest that the IVD model should be optimized to mimic NPD at the transcriptomic level. Our study contributes to an increase in the knowledge about mouse models of decidualization.

Follistatin is a crucial chemoattractant for mouse decidualized endometrial stromal cell migration by JNK signalling

“… 14 , 33 Vimentin as a marker of stromal cells is highly expressed in stromal cells no matter decidualization happens or not, 34 and prolactin is widely used as a decidualization marker. 35 , 36 …”

“…Decidualization initially occurs in ESCs around the spiral arteries and spreads to the whole endometrium once pregnancy occurs 14,33 . Vimentin as a marker of stromal cells is highly expressed in stromal cells no matter decidualization happens or not, 34 and prolactin is widely used as a decidualization marker 35,36 …”

Decidualization and Related Pregnancy Complications

“…(2) primary mouse ESCs can only divide 2-3 times in vitro and a longer time of IVD causes abnormal morphological changes likely due to replicative senescence; and (3) the addition of cAMP analogs (EPC scheme) is no better than E2 combined P4 scheme to induce IVD in mice. 14…”

Identification of Intercellular Crosstalk between Decidual Cells and Niche Cells in Mice

“…Slightly different from humans, the decidual reaction in mice is an embryo-dependent process. Prolactin family 8 subfamily a member 2 (Prl8a2), a paralog of human dPRL, is a well-established marker for mouse decidualization [ 5 ]. By using uterus-specific gene knockout mice, a number of genes have been proved to be required for decidualization [ 6 ].…”

“…By using uterus-specific gene knockout mice, a number of genes have been proved to be required for decidualization [ 6 ]. Alternatively, several studies have analyzed global gene expression changes associated with decidualization by using high-throughput transcriptomic approaches [ 5 , 7 , 8 , 9 , 10 ]. The limitation of these studies is that the bulk tissue was used.…”