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.
Highlights
Endometrial stromal cell decidualization is a prerequisite for embryo implantation and pregnancy in human reproduction [1]
Insufficient decidualization may lead to repeated pregnancy loss (RPL), intrauterine growth restriction (IUGR), and severe pre-eclampsia [5]
By using RNA-seq, we investigated the global gene expression profiles of 3 mouse models of decidualization: natural pregnancy decidualization on day 8 of pregnancy (NPD), artificial decidualization of mouse uterus stimulated by sesame oil (AD), and in vitro decidualization of cultured stromal cells by incubation with estrogen plus progesterone (IVD)
Summary
Endometrial stromal cell decidualization is a prerequisite for embryo implantation and pregnancy in human reproduction [1]. Decidualization is a spontaneous process, which initiates in the secretory phase of the menstrual cycle controlled by ovarian steroid hormones [2]. During this process, endometrial stromal cells change into large epithelioid cells and secrete two protein markers, decidual prolactin (dPRL) and insulin-like growth factor-binding protein 1 (IGFBP1) [3]. Decidualization plays important roles in embryonic implantation, placentation, and pregnancy maintenance [4]. Insufficient decidualization may lead to repeated pregnancy loss (RPL), intrauterine growth restriction (IUGR), and severe pre-eclampsia (sPE) [5].
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