Gene Expression Profiling of Human Endometrial-Trophoblast Interaction in a Coculture Model

Popovici, R.; Betzler, Nina Katrin; Krause, M.; Luo, Meiling; Jauckus, Julia; Germeyer, Ariane; Bloethner, Sandra; Schlotterer, Andreas; Kumar, Rajiv; Strowitzki, T.; Wolff, Michael von

doi:10.1210/en.2006-0916

Cited by 116 publications

(85 citation statements)

References 54 publications

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“…More recently, gene expression profiling of hESCs has shown that levels of many hESC mRNAs are modulated in response to trophoblast-conditioned medium (23) or after coculture with firsttrimester trophoblast explants (34), further corroborating the concept of embryo-mediated modulation of endometrial cell gene expression. Here, we have demonstrated that in vitro, the human embryo induces changes in hESC RacGAP1 expression levels.…”

Section: Discussionmentioning

confidence: 79%

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.

162

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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Section: Discussionmentioning

confidence: 79%

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.

162

140

View full text Add to dashboard Cite

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“…Many ISGs induced by IFNT in ruminants (see Spencer et al 2007) are among the most upregulated genes in human endometrial stromal cells co-cultured with human trophoblast (Popovici et al 2006) or treated with human trophoblast-conditioned medium (Hess et al 2007) and in endometria of baboons, domestic animals, and laboratory animals (see Bazer et al 2008Bazer et al , 2009…”

Section: Maternal Recognition Of Pregnancymentioning

confidence: 99%

Comparative aspects of implantation

Bazer

Spencer²,

Johnson³

et al. 2009

Reproduction

337

285

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Uterine receptivity to implantation of blastocysts in mammals includes hatching from zona pellucida, precontact with uterine luminal (LE) and superficial glandular (sGE) epithelia and orientation of blastocyst, apposition between trophectoderm and uterine LE and sGE, adhesion of trophectoderm to uterine LE/sGE, and, in some species, limited or extensive invasion into the endometrial stroma and induction of decidualization of stromal cells. These peri-implantation events are prerequisites for pregnancy recognition signaling, implantation, and placentation required for fetal-placental growth and development through the remainder of pregnancy. Although there is a range of strategies for implantation in mammals, a common feature is the requirement for progesterone (P 4 ) to downregulate expression of its receptors in uterine epithelia and P 4 prior to implantation events. P 4 then mediates its effects via growth factors expressed by stromal cells in most species; however, uterine luminal epithelium may express a growth factor in response to P 4 and/or estrogens in species with a true epitheliochorial placenta. There is also compelling evidence that uterine receptivity to implantation involves temporal and cell-specific expression of interferon (IFN)-stimulated genes that may be induced directly by an IFN or induced by P 4 and stimulated by an IFN. These genes have many roles including nutrient transport, cellular remodeling, angiogenesis and relaxation of vascular tissues, cell proliferation and migration, establishment of an antiviral state, and protection of conceptus tissues from challenges by the maternal immune cells.

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“…In vitro models such as decidualized stromal cells treated with conditioned media from trophoblasts and an in vitro co-culture system of endometrial stromal cells with the first-trimester trophoblast explants revealed upregulation of mPGES-1 (PTGES) in human endometrial cells (Popovici et al 2006, Hess et al 2007. Moreover, a recent study showed that the human embryonic signal, chorionic gonadotropin, regulates the mPGES-1 promoter and induces mPGES-1 synthesis in endometrial epithelial cells via the PI3K-ERK1/2 pathway (Banerjee et al 2009).…”

Section: Some New Insights On Pg Synthesis During Early Pregnancy In mentioning

confidence: 99%

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

Wacławik

2011

Reproduction

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Ovarian progesterone induces essential changes leading to a temporary state of uterine receptivity for conceptus implantation. Estrogens secreted by the porcine conceptus on days 11 and 12 of pregnancy provide the initial signal for maternal recognition of pregnancy and maintenance of a functional corpus luteum (CL) for continued production of progesterone. As prostaglandins F 2a (PGF 2a ) and E 2 (PGE 2 ) exert opposing actions on the CL, a tight control over their synthesis and secretion is critical either for the initiation of luteolysis or maintenance of pregnancy. One of the supportive mechanisms by which conceptus inhibits luteolysis is changing PG synthesis in favor of luteoprotective PGE 2 . Conceptus PGE 2 could be amplified by PGE 2 feedback loop in the endometrium. In pigs, as in other species, implantation and establishment of pregnancy is associated with upregulation of expression of proinflammatory factors, which include cytokines, growth factors, and lipid mediators. The conceptus produces inflammatory mediators: interferon g and interferon d, interleukins IL1B and IL6, and PGs, which probably activate inflammatory pathways in the endometrium. The endometrium responds to these embryonic signals by enhancing further progesterone-induced uterine receptivity. Understanding the mechanisms of pregnancy establishment is required for translational research to increase reproductive efficiencies and fertility in humans and animals.

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Gene Expression Profiling of Human Endometrial-Trophoblast Interaction in a Coculture Model

Cited by 116 publications

References 54 publications

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

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

Comparative aspects of implantation

Novel insights into the mechanisms of pregnancy establishment: regulation of prostaglandin synthesis and signaling in the pig

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