Abstract
BackgroundEarly pregnancy failure has a profound impact on both human reproductive health and animal production. 2/3 pregnancy failures occur during the peri-implantation period; however, the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy. Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss.ResultIn this study, using well-managed recipient ewes that received embryo transfer as model, we compared the endometrial proteome between pregnant and non-pregnant ewes during implantation period. After embryo transfer, recipients were assigned as pregnant or non-pregnant ewes according to the presence or absence of an elongated conceptus at Day 17 of pregnancy. By comparing the endometrial proteomic profiles between pregnant and non-pregnant ewes, we identified 94 and 257 differentially expressed proteins (DEPs) in the endometrial caruncular and intercaruncular areas, respectively. Functional analysis showed that the DEPs were mainly associated with immune response, nutrient transport and utilization, as well as proteasome-mediated proteolysis.ConclusionThese analysis imply that dysfunction of these biological processes or pathways of DEP in the endometrium is highly associated with early pregnancy loss. In addition, many proteins that are essential for the establishment of pregnancy showed dysregulation in the endometrium of non-pregnant ewes. These proteins, as potential candidates, may contribute to early pregnancy loss.Electronic supplementary materialThe online version of this article (doi:10.1186/s40104-015-0017-0) contains supplementary material, which is available to authorized users.
Highlights
Pregnancy loss in livestock and humans is estimated to occur in 20 to 40% of pregnancies [1], two-thirds of which occur during the peri-implantation period [2,3]
Many dysregulated proteins were identified in the endometrium of non-pregnant ewes, some of which had been reported to be involved in establishment of pregnancy, while the roles of other newly identified proteins in early pregnancy failure remain to be further investigated
Based on the functional enrichment analysis of differentially expressed proteins (DEPs) by GO, KEGG and network categories, a general conclusion can be drawn that aberrant nutrient transport and utilization, abnormal immune responses, as well as aberrant proteasomedependent proteolysis in the endometrium are tightly associated with early pregnancy failure in sheep (Figure 5A)
Summary
Pregnancy loss in livestock and humans is estimated to occur in 20 to 40% of pregnancies [1], two-thirds of which occur during the peri-implantation period [2,3]. Implantation, a critical event for establishing pregnancy, involves an elaborate set of molecules essential to maternal–fetal crosstalk. Despite many previous studies on factors involved in early pregnancy loss, the underlying mechanism(s) remains unclear. The ‘-omic’ approaches, including RNA-seq, microarray and proteomic profiling, have been used to profile the gene or protein expression patterns in the endometrium during peri-implantation period. Mansouri-Attia showed gene expression patterns in the bovine endometrium during early pregnancy after artificial insemination (AI) using microarray analysis [7]. 2/3 pregnancy failures occur during the peri-implantation period; the underlying mechanism(s) remains unclear. Well-organized modification of the endometrium to a receptive state is critical to establish pregnancy. Aberrant endometrial modification during implantation is thought to be largely responsible for early pregnancy loss
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