It is one of the important events that trophoblast cells within the placental folds differentiate into two types that differ in cell shape during placental development in pigs. This study showed that all the trophoblast cells were of similar shape between Yorkshire and Chinese Meishan pigs on day 26 of gestation; thereafter, the trophoblast cells located at the top of the placental folds became high columnar, while those cells at the base of the placental folds were cuboidal on day 50 of gestation. Additionally, on day 95 of gestation, all the trophoblast cells in Meishan pigs became cuboidal, but the trophoblast cells located at the top of the placental folds in Yorkshire pigs still remained columnar. The membranous E-cadherin and β-catenin were strongly co-expressed by the high columnar trophoblast cells but very weakly expressed by those cuboidal cells. Consistently, the expression pattern of ZEB2, the E-cadherin repressor, was inversely correlated with that of E-cadherin in the two types of trophoblast cells in the two breeds. Furthermore, electrophoretic mobility shift assays demonstrated the binding of ZEB2 to the E-cadherin promoter in nuclear extracts from porcine placental tissue. These findings suggest a ZEB2-dependent mechanism of trophoblast cell differentiation during placental development in pigs.
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- Author: Linjun Hong x
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Linjun Hong, Kun Han, Kejia Wu, Ruize Liu, Ji Huang, Joan K Lunney, Shuhong Zhao, and Mei Yu
Yan Sun, Yifen Yang, Ziran Jiang, Feiyu wang, Kun Han, Linjun Hong, Jianhua Cao, and Mei Yu
In brief
Transforming the endometrial luminal epithelium (LE) into a receptive state is a requisite event for successful embryo implantation. This study suggests the role of a transcription factor in regulating endometrial LE receptivity.
Abstract
The endometrial luminal epithelium (LE) undergoes extensive remodeling during implantation to establish receptivity of the uterus in response to the conceptus signals, such as interleukin 1β (IL1B). But the mechanisms remain to be fully understood. This study investigated the role of CCAAT/enhancer-binding protein β (C/EBP-β) in regulating pig endometrial LE receptivity. Our results showed that C/EBP-β was expressed and activated only in the endometrial LE in an implantation-dependent manner. In addition, C/EBP-β was highly activated at the pre-attachment stage compared to the attachment stage, and its activation was correlated with the expression of IL1B-dependent extracellular signal-regulated kinases1/2-p90 ribosomal S6 kinase signaling axis. Subsequent chromatin immunoprecipitation (ChIP)-sequencing analysis revealed that the binding of C/EBP-β within the promoter was positively associated with the transcription of genes related to cell remodeling. One such gene is matrix metalloproteinase 8 (MMP8), which is responsible for extracellular matrix degradation. The expression of MMP8 was abundant at the pre-attachment stage but dramatically declined at the attachment stage in the endometrial LE. Consistent with C/EBP-β, the expression and activation of MMP8 were limited to the endometrial LE in an implantation-dependent manner. Using ChIP-qPCR and electrophoresis mobility shift assay approaches, we demonstrated that C/EBP-β regulated the expression of the MMP8 gene during implantation. Furthermore, we detected that MMP8 and one of its substrates, type II collagen, showed a mutually exclusive expression pattern in pig endometrial LE during implantation. Our findings indicate that C/EBP-β plays a role in pig endometrial LE receptivity by regulating cell remodeling-related genes, such as MMP8, in response to conceptus signals during implantation.
