Abstract

The endometrial luminal epithelium (LE) undergoes extensively remodeling during implantation to establish receptivity of the uterus in response to the conceptus signals, such as interleukin 1β (IL-1β). 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 IL-1β-dependent ERK1/2-P90RSK signaling axis. Subsequent ChIP-seq 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 (MMP-8), which is responsible for extracellular matrix degradation. The expression of MMP-8 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 MMP-8 were limited to the endometrial LE in an implantation-dependent manner. Using ChIP-qPCR and EMSA approaches, we demonstrated that C/EBP-β regulated the expression of the MMP-8 gene during implantation. Furthermore, we detected that MMP-8 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 MMP-8, in response to conceptus signals during implantation.