Abstract
BackgroundImplantation failure limits the success of in vitro fertilization and embryo transfer (IVF-ET). Well-organized embryo-maternal crosstalk is essential for successful implantation. Previous studies mainly focused on the aberrant development of in vitro fertilized (IVF) embryos. In contrast, the mechanism of IVF-induced aberrant embryo-maternal crosstalk is not well defined.ResultsIn the present study, using ewes as the model, we profiled the proteome that features aberrant IVF embryo-maternal crosstalk following IVF-ET. By comparing in vivo (IVO) and IVF conceptuses, as well as matched endometrial caruncular (C) and intercaruncular (IC) areas, we filtered out 207, 295, and 403 differentially expressed proteins (DEPs) in each comparison. Proteome functional analysis showed that the IVF conceptuses were characterized by the increased abundance of energy metabolism and proliferation-related proteins, and the decreased abundance of methyl metabolism-related proteins. In addition, IVF endometrial C areas showed the decreased abundance of endometrial remodeling and redox homeostasis-related proteins; while IC areas displayed the aberrant abundance of protein homeostasis and extracellular matrix (ECM) interaction-related proteins. Based on these observations, we propose a model depicting the disrupted embryo-maternal crosstalk following IVF-ET: Aberrant energy metabolism and redox homeostasis of IVF embryos, might lead to an aberrant endometrial response to conceptus-derived pregnancy signals, thus impairing maternal receptivity. In turn, the suboptimal uterine environment might stimulate a compensation effect of the IVF conceptuses, which was revealed as enhanced energy metabolism and over-proliferation.ConclusionSystematic proteomic profiling provides insights to understand the mechanisms that underlie the aberrant IVF embryo-maternal crosstalk. This might be helpful to develop practical strategies to prevent implantation failure following IVF-ET.
Highlights
Implantation failure limits the success of in vitro fertilization and embryo transfer (IVF-ET)
As expected, unsupervised hierarchical clustering of the protein intensity profiles revealed that the endometrial C and IC areas clustered closely together, and the cluster expanded to the conceptuses in in vivo (IVO) or in vitro fertilized (IVF) groups (Additional file 1: Figure S1C)
No detectable changes were observed in the level of DNA methyltransferases (DNMTs), we found that the abundance of methyl metabolism-related proteins, such as SHMT2, MTHFD1, AHCY, and METTL7A, which catalyze key steps of methyl metabolism and transfer, decreased in the IVF conceptuses (Fig. 2d), For example, folic acid is the methyl donor of s-adenosylmethionine (SAM), and SAM is the unique active methyl donor of the DNA methylation process
Summary
Implantation failure limits the success of in vitro fertilization and embryo transfer (IVF-ET). Aiming to improve the IVF success rate, numerous studies have been performed that focused on the mechanisms responsible for impaired development potential of IVF embryos, including many genetic and cellular changes, such as epigenetic modifications [8, 9], genetic information processing [10], energy metabolism [11], and cytoskeleton organization [12]. Based on these observations, strategies have been applied to correct these aberrations, enhancing IVF embryo developmental potential [9, 12,13,14,15]
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