Review of factors essential for blastocyst implantation for their modulating effects on the maternal immune system

Reproductive Sciences Branch, Center for Population Research, National Institute of Child Health and Human Development, NIH, DHHS, Bethesda, MD 20892-7510, USA.
Seminars in Cell and Developmental Biology (Impact Factor: 6.27). 05/2008; 19(2):161-9. DOI: 10.1016/j.semcdb.2007.10.006
Source: PubMed

ABSTRACT Pituitary and ovarian hormones prepare the endometrium for successful blastocyst implantation and support its process directly or indirectly through the action of growth factors, cytokines and other molecules. Many of the blastocyst implantation essential factors (BIEFs) are modulators of the maternal immune system. Since little is known as to the action of these molecules on the uterine lymphocytes, its clarification is imperative to the understanding of the process of blastocyst implantation.

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    • "Once materno-zygotic contact is established, the trophectoderm cells invade into the luminal epithelium [3]. Numerous factors, such as hormones, growth factors, cytokines, vasoactive agents, etc., have been identified, which appear to play an essential role during implantation [4, 5]. The importance of implantation in reproduction is exemplified by the fact that loss of function of genes such as HOX [6] and COX2 [7], which are essential for implantation, leads to infertility. "
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    ABSTRACT: Luman/CREB3 recruitment factor (LRF or CREBRF) was identified as a regulator of Luman (or CREB3) that is involved in the unfolded protein response during endoplasmic reticulum stress. Luman is implicated in a multitude of functions ranging from viral infection and immunity to cancer. The biological function of LRF, however, is unknown. In this paper, we report that uteri of pregnant mice and embryos displayed enhanced LRF expression at all stages, and the expressed LRF was found to be localized specifically at implantation sites. On the other hand, uteri of mice induced for delayed implantation or pseudopregnant mice showed low levels of LRF expression, suggesting that LRF mediates uterine receptivity during implantation. Further, expression of LRF was found to be modulated by steroid hormones such as progesterone and estradiol. This study thereby identifies a potential role for LRF in the process of implantation in uteri and development of preimplantation embryos in mice.
    Journal of Reproduction and Development 02/2013; 59(3). DOI:10.1262/jrd.2012-137 · 1.52 Impact Factor
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    • "A yet unknown proportion of implantation failure in IVF might be due to yet undiscovered endometrial defects (Horcajadas et al., 2007, 2008; Aghajanova et al., 2008; Oehninger, 2008). But so far, neither the key molecules involved, nor their strict localization and temporal variations are well known and therefore, the possibility for clinical intervention is limited (Dey et al., 2004; Yoshinaga, 2008). Studies focusing on early human implantation have been largely descriptive. "
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    ABSTRACT: There is an urgent need to develop optimized experimental models to examine human implantation. These studies aimed to (i) establish a human endometrium-like three-dimensional (3D) culture system, and (ii) examine the attachment of trophoblast-like Jar spheroids to the culture. In the present work, 3D endometrial cultures were constructed with fibrin-agarose as matrix scaffold, and using epithelial and stromal cells from both human primary cultures and established cell lines. An attachment assay between trophoblast cells and the 3D culture was developed. Epithelial cells (cytokeratin(+)) concentrated on top of the matrix forming a monolayer, and stromal cells (vimentin(+)) resided within the matrix, resembling the normal endometrial structure. The capability of primary epithelial cells to form glands spontaneously was observed. Human trophoblast cells (Jar cells) were hCG(+) by immunostaining, allowed to form spheroids, and confirmed to secrete hCG into the medium. Time-dependent experiments demonstrated a high rate of attachment of Jar spheroids to the epithelium, and adhesion was strongly related to the various cell types present in the 3D culture. An architecturally and functionally competent 3D endometrial culture system was established, that coupled with Jar spheroids mimicking trophoblast cells, provides a unique in vitro model for the study of certain aspects of human implantation.
    Molecular Human Reproduction 01/2012; 18(1):33-43. DOI:10.1093/molehr/gar064 · 3.75 Impact Factor
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    • "It is becoming particularly evident that implantation is an inflammatory event and that proinflammatory signals are required for the establishment of a receptive endometrium (Jabbour et al. 2009). Increased levels of pro-inflammatory cytokines, induced by paracrine signaling from the embryo, characterize the endometrium during early implantation (Koga and Mor, 2008; Mor and Koga, 2008; Yoshinaga, 2008) and are believed to signal upregulation of proteins required for embryo receptivity, adhesion and invasion (Evans et al. 2009; Jabbour et al. 2009; Sherwin et al. 2007). In the Fallopian tube, it is a pro-inflammatory phenotype caused by tubal damage from infection and or smoking, which is it believed to cause upregulation of pro-inflammatory cytokines which induce factors promoting embryo receptivity, adhesion and invasion, leading to ectopic pregnancy. "
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    ABSTRACT: As part of successful human reproduction, the Fallopian tube must provide a suitable environment for pre-implantation development of the embryo and for efficient transport of the embryo to the uterus for implantation. These functions are coordinated by paracrine interactions between tubal epithelial, smooth muscle and immune cells and the cells of the developing embryo. Alterations in these signals can lead to a tubal microenvironment encouraging of embryo implantation and to dysregulated tubal motility, ultimately resulting in inappropriate and early implantation of the embryo in the Fallopian tube. Here, we highlight novel and emerging concepts in tubal physiology and pathobiology, such as the induction of a receptive phenotype within the Fallopian tube, leading to ectopic implantation. Chlamydia trachomatis infection is a risk factor for tubal ectopic pregnancy. Activation of toll-like receptor 2 (TLR-2) in the Fallopian tube epithelium, by C. trachomatis has recently been demonstrated, leading to the dysregulation of factors involved in implantation and smooth muscle contractility, such as prokineticins (PROK), activin A and interleukin 1 (IL-1). The Fallopian tube has also recently been shown to harbour a unique population of immune cells, compared to the endometrium. In addition, the complement of immune cells in the Fallopian tube has been reported to be altered in Fallopian tube from women with ectopic pregnancy. There are increasing data suggesting that vascularisation of the Fallopian tube, by the embryo during ectopic pregnancy, differs from that initiated in the uterus during normal pregnancy. This too, is likely the result of paracrine signals between the embryo and the tubal microenvironment.
    Molecular and Cellular Endocrinology 07/2011; 358(2):216-22. DOI:10.1016/j.mce.2011.07.037 · 4.41 Impact Factor
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