Integration of molecules to construct the processes of conceptus implantation to the maternal endometrium

Abstract

During the peri-implantation period, ruminant conceptuses go through rapid elongation, followed by their attachment to the uterine endometrial epithelial cells, during which interferon-tau (IFNT), a trophectodermal cytokine required for the process of maternal recognition of pregnancy, is expressed in a temporal and spatial manner. On day 22 (day 0 = day of estrus), 2 to 3 d after the initiation of bovine conceptus attachment to the uterine epithelium, when IFNT production begins to subside, the expression of molecules related to epithelial-mesenchymal transition, zinc finger E-box binding homeobox 1, snail family transcriptional repressor 2, N-cadherin, and vimentin was found in the trophectoderm. Through the use of in vitro coculture system with bovine trophoblast CT-1 and endometrial epithelial cells, a series of experiments have been conducted to elucidate mechanisms associated with the regulation of IFNT gene transcription and conceptus implantation, including epithelial-mesenchymal transition processes. Expression of IFNT, both up- and downregulation, during the peri-implantation period is tightly controlled. Cytokines and cell adhesion molecules such as epidermal growth factor, basic fibroblast growth factor, transforming growth factor beta, activin A, L-selectin-podocalyxin, and vascular cell adhesion molecule 1-integrin α4 expressed in utero all contribute to the initiation of epithelial-mesenchymal transition in the trophectoderm. These results indicate that conceptus implantation to the uterine endometrium proceeds while elongated conceptuses and endometria express cell adhesion molecules and their receptors, and the trophectoderm experiences epithelial-mesenchymal transition. Data accumulated suggest that while the conceptus and the endometrial epithelium adhere, trophectodermal cells must gain more flexibility for binucleate and possibly trinucleate cell formation during the peri-implantation period, and that understanding and constructing the conditions throughout implantation processes is key to improving ruminants' fertility.