Fine-tuned adaptation of embryo–endometrium pairs at implantation revealed by transcriptome analyses in Bos taurus

Abstract

Interactions between embryo and endometrium at implantation are critical for the progression of pregnancy. These reciprocal actions involve exchange of paracrine signals that govern implantation and placentation. However, it remains unknown how these interactions between the conceptus and the endometrium are coordinated at the level of an individual pregnancy. Under the hypothesis that gene expression in endometrium is dependent on gene expression of extraembryonic tissues and genes expressed in extraembryonic tissues are dependent of genes expressed in the endometrium, we performed an integrative analysis of transcriptome profiles of paired extraembryonic tissue and endometria obtained from cattle ( Bos taurus ) pregnancies initiated by artificial insemination. We quantified strong dependence (|r| > 0.95, empirical false discovery rate [eFDR] < 0.01) in transcript abundance of genes expressed in the extraembryonic tissues and genes expressed in the endometrium. The profiles of connectivity revealed distinct coexpression patterns of extraembryonic tissues with caruncular and intercaruncular areas of the endometrium. Notably, a subset of highly coexpressed genes between extraembryonic tissue ( n = 229) and caruncular areas of the endometrium ( n = 218, r > 0.9999, eFDR < 0.001) revealed a blueprint of gene expression specific to each pregnancy. Gene ontology analyses of genes coexpressed between extraembryonic tissue and endometrium revealed significantly enriched modules with critical contribution for implantation and placentation, including “in utero embryonic development,” “placenta development,” and “regulation of transcription.” Coexpressing modules were remarkably specific to caruncular or intercaruncular areas of the endometrium. The quantitative association between genes expressed in extraembryonic tissue and endometrium emphasize a coordinated communication between these two entities in mammals. We provide evidence that implantation in mammalian pregnancy relies on the ability of the extraembryonic tissue and the endometrium to develop a fine-tuned adaptive response characteristic of each pregnancy.

Isolation and Characterization of Equine Uterine Extracellular Vesicles: A Comparative Methodological Study

“…For example, ADH5 was not identified by trehalose method (MD_CE/TRE) but with relatively high intensity in all three replicates of MC in the comparison ME vs. MC. ADH5 gene expression has been found in intercaruncular tissues in bovine [ 70 ] and also identified in the uterine fluid proteome of roe deer [ 71 ], where it may play a role in cellular detoxification before implantation. Besides, the use of trehalose in the EVs isolation protocol allowed or improved the identification of other proteins including PAK2, LAMB2 and SEMA4B, which may play an important role in uterine functions and embryo development.…”

Embryo biosensing by uterine natural killer cells determines endometrial fate decisions at implantation

“…Evidence from multiple mammalian species indicates that the endometrium is capable of mounting an implantation response tailored to the developmental potential of individual embryos. 21,[51][52][53] In humans, directed migration of decidualizing EnSC and active encapsulation of the conceptus constitutes an important initial step in the implantation process. 52 In vitro studies demonstrated that high-quality human embryos stimulate migration of decidual cells, whereas low-quality embryos fail to do so.…”

“…21,[51][52][53] In humans, directed migration of decidualizing EnSC and active encapsulation of the conceptus constitutes an important initial step in the implantation process. 52 In vitro studies demonstrated that high-quality human embryos stimulate migration of decidual cells, whereas low-quality embryos fail to do so. Conversely, migration of undifferentiated EnSC is actively inhibited by high-quality embryos, but not low-quality embryos.…”

Involvement of uterine natural killer cells in the natural selection of human embryos at implantation

“…21,48–50 In humans, directed migration of decidualizing EnSC and active encapsulation of the conceptus constitutes an important initial step in the implantation process. 49 In vitro studies demonstrated that high-quality human embryos stimulate migration of decidual cells whereas low-quality embryos fail to do so. Conversely, migration of undifferentiated EnSC is actively inhibited by high-quality embryos, but not low-quality embryos.…”