Animal models of implantation

Lee, Kevin Y.; DeMayo, Francesco J.

doi:10.1530/rep.1.00340

Cited by 232 publications

(166 citation statements)

References 204 publications

(118 reference statements)

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“…The invasion of the endometrium by fetal tissue is very limited in ruminants, resulting in a synepitheliochorial structure of the placenta (39). Given the ready access to conceptus tissues and well described developmental processes, ruminants are considered an exceptional model in which to study apposition and attachment during implantation (40). A critical feature of implantation is the coordination of molecular signals with the endometrium during the periimplantation period (1).…”

Section: Discussionmentioning

confidence: 99%

Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium

Biase

Rabel

Guillomot

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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A major unresolved issue in the cloning of mammals by somatic cell nuclear transfer (SCNT) is the mechanism by which the process fails after embryos are transferred to the uterus of recipients before or during the implantation window. We investigated this problem by using RNA sequencing (RNA-seq) to compare the transcriptomes in cattle conceptuses produced by SCNT and artificial insemination (AI) at day (d) 18 (preimplantation) and d 34 (postimplantation) of gestation. In addition, endometrium was profiled to identify the communication pathways that might be affected by the presence of a cloned conceptus, ultimately leading to mortality before or during the implantation window. At d 18, the effects on the transcriptome associated with SCNT were massive, involving more than 5,000 differentially expressed genes (DEGs). Among them are 121 genes that have embryonic lethal phenotypes in mice, cause defects in trophoblast and placental development, and/or affect conceptus survival in mice. In endometria at d 18, <0.4% of expressed genes were affected by the presence of a cloned conceptus, whereas at d 34, ∼36% and <0.7% of genes were differentially expressed in intercaruncular and caruncular tissues, respectively. Functional analysis of DEGs in placental and endometrial tissues suggests a major disruption of signaling between the cloned conceptus and the endometrium, particularly the intercaruncular tissue. Our results support a "bottleneck" model for cloned conceptus survival during the periimplantation period determined by gene expression levels in extraembryonic tissues and the endometrial response to altered signaling from clones. somatic cell nuclear transfer | conceptus | placentation | conceptus-maternal communication I n cattle, as in other mammals, exquisitely orchestrated physiological changes of the conceptus and uterus are necessary for a successful pregnancy. Synchronization of the complex events at the time of implantation relies on the timed release of molecular signals from the conceptus and the endometrium. Embryo-derived IFN-τ (IFNT) is the major signal of pregnancy in cattle, preventing luteolysis and regulating the expression of genes that are responsible for promoting local changes in the endometrium to accommodate the conceptus (1-3). In females, progesterone is the major driver of endometrial changes that prepare the uterus for conceptus implantation (4, 5). In addition to IFNT and progesterone, signaling between the bovine conceptus and the endometrium is bidirectional, and involves several pathways that work concomitantly (6) for the successful establishment of pregnancy.Independent studies have shown that the majority of embryonic losses in cattle occur during the period that spans embryo cleavage until the attachment of the blastocyst to the endometrium (7). The reasons for these losses remain unclear and likely result from several factors, including embryonic lethal genes (8, 9), environmental stressors (7), and endometrial condition (10). Cloning of cattle by somatic cell nuclear transfer ...

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Section: Discussionmentioning

confidence: 99%

Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium

Biase

Rabel

Guillomot

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Developing an understanding of mouse biology, the characteristics of the mouse strains to be used and the biology of the target species will aid in the proper use of the mouse as a model. Comparison of the timing of significant events in embryo development in humans, cattle and mice [21] and adapted from Menezo and Herubel 2002 [11].…”

Section: Discussionmentioning

confidence: 99%

“…Given the differences in implantation strategies among these species, the mouse has limited utility as a model for studying the physiology of implantation in cattle or humans. However, there is some commonality across these species, as implantation is controlled by ovarian steroids and many of the same growth factors and cytokines, making the mouse a useful model for examining the control of implantation [21].…”

Section: Implantationmentioning

confidence: 99%

Virtues and limitations of the preimplantation mouse embryo as a model system

Taft

2008

Theriogenology

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The mouse is the most widely used model of preimplantation embryo development, but is it a good model? Its small size, prolificacy and ease of handling make the mouse a relatively low cost, readily available and attractive alternative when embryos from other species are difficult or expensive to obtain. However, the real power of the mouse as a model lies in mouse genetics. The development of inbred mouse strains facilitated gene discovery as well as our understanding of gene function and regulation while the development of tools to introduce precise genetic modifications uniquely positioned the mouse as a powerful model system for uncovering gene function. However, all models have limitations; the small size of the mouse limits tissue availability and manipulations that can be performed and differences in physiology among species may make it inappropriate to extrapolate from the mouse to other species. Thus, rather than extrapolating directly from the mouse to other species, it may be more useful to use the mouse as a model system for developing and refining hypotheses to be tested directly in species of interest. In this brief review, the value of the preimplantation mouse embryo as a model is considered, both as a model for other species and as a model for the mouse, as understanding the virtues and limitations of the mouse as a model system is essential to its appropriate use.

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“…Mouse models have provided valuable insights into the molecular mechanisms that occur during embryo implantation (7); however, these models do not necessarily translate to the human because the reproductive physiology of mice and humans is different (8). We have developed an in vitro model that recapitulates the early steps of human embryonic trophoblast invasion into the stroma during embryo implantation (9).…”

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confidence: 99%

Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration

Grewal

Carver

Ridley

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

165

140

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Failure of the human embryo to implant into the uterine wall during the early stages of pregnancy is a major cause of infertility. Implantation involves embryo apposition and adhesion to the endometrial epithelium followed by penetration through the epithelium and invasion of the embryonic trophoblast through the endometrial stroma. Although gene-knockdown studies have highlighted several molecules that are important for implantation in the mouse, the molecular mechanisms controlling implantation in the human are unknown. Here, we demonstrate in an in vitro model for human implantation that the Rho GTPases Rac1 and RhoA in human endometrial stromal cells modulate invasion of the human embryo through the endometrial stroma. We show that knockdown of Rac1 expression in human endometrial stromal cells inhibits human embryonic trophoblast invasion into stromal cell monolayers, whereas inhibition of RhoA activity promotes embryo invasion. Furthermore, we demonstrate that Rac1 is required for human endometrial stromal cell migration and that the motility of the stromal cells increases at implantation sites. This increased motility correlates with a localized increase in Rac1 activation and a reciprocal decrease in RacGAP1 levels. These results reveal embryo-induced and localized endometrial responses that may govern implantation of the human embryo.human trophoblast invasion ͉ implantation in vitro ͉ Rac-1 activation ͉ RacGAP1 ͉ Rho GTPases

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Animal models of implantation

Cited by 232 publications

References 204 publications

Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium

Massive dysregulation of genes involved in cell signaling and placental development in cloned cattle conceptus and maternal endometrium

Virtues and limitations of the preimplantation mouse embryo as a model system

Implantation of the human embryo requires Rac1-dependent endometrial stromal cell migration

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