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      Delineating the prime mover action of progesterone for endometrial receptivity in primates

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          Abstract

          Progesterone is essential for endometrial receptivity in primates. It is now evident that embryo-derived signal influences implantation stage endometrium under progesterone dominance, and collectively results in endometrial receptivity to implanting blastocyst. Previously, a few studies were performed using global gene profiling based on microarray technology to identify changes in gene expression between early luteal phase and mid luteal phase endometrium, however, the issue of combinatorial regulation by progesterone-dependent regulation and by embryo-derived signal on transcripts profiles during endometrial differentiation toward receptivity for blastocyst implantation in primates has not been addressed. The present review summarizes a few issues, specifically that of transforming growth factor β-tumour necrosis factor α (TGFβ-TNFα) pathways and signal transducer and activator of transcription (STAT) signalling system related to luteal phase progesterone action on endometrial receptivity in terms of its transcriptomic expression using a potent antiprogestin (mifepristone) in conception cycles of the rhesus monkey as a non-human primate model.

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          Most cited references52

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          TGF-beta induces bimodal proliferation of connective tissue cells via complex control of an autocrine PDGF loop.

          Transforming growth factor-beta (TGF-beta) acts as a growth inhibitor, yet it can stimulate proliferation; 1-2 fg/cell of TGF-beta 1 elicits maximal proliferation of dense and sparse cultured smooth muscle cells (SMCs), whereas higher amounts are less stimulatory. This bimodal response is not limited to SMCs, as TGF-beta induces a similar response in human fibroblasts and chondrocytes. The amount of TGF-beta 1 per cell that induces maximal proliferation is identical for dense and sparse SMCs. At low concentrations of TGF-beta, there is a 10-12 hr delay in DNA synthesis compared with that elicited by PDGF. PDGF-AA is detected in the culture medium at 24 hr, and anti-PDGF IgG blocks DNA synthesis. At higher concentrations, TGF-beta 1 decreases transcripts and expression of PDGF receptor alpha subunits. Hence, TGF-beta induces proliferation of connective tissue cells at low concentrations by stimulating autocrine PDGF-AA secretion, which at higher concentrations of TGF-beta, is decreased by down-regulation of PDGF receptor alpha subunits and perhaps by direct growth inhibition.
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            Endothelial Cells Require STAT3 for Protection against Endotoxin-induced Inf lammation

            Endothelial cells (ECs) are believed to be an important component in the protection from lipopolysaccharide (LPS)-induced endotoxic shock. However, the cellular and molecular mechanism is not well defined. Here, we report that signal transducer and activator of transcription (STAT) 3 is an essential regulator of the antiinflammatory function of ECs in systemic immunity. Because STAT3 deficiency results in early embryonic lethality, we have generated mice with a conditional STAT3 deletion in endothelium (STAT3E−/−). STAT3E−/− mice are healthy and fertile, and isolated ECs initiate normal tube formation in vitro. Conditional endothelial but not organ-specific (i.e., hepatocyte or cardiomyocyte) STAT3 knockout mice show an increased susceptibility to lethality after LPS challenge. The LPS response in STAT3E−/− mice shows exaggerated inflammation and leukocyte infiltration in multiple organs combined with elevated activity of serum alanine aminotransferase and aspartate aminotransferase, indicating organ damage. Concomitantly, proinflammatory cytokines are produced at an exaggerated level and for a prolonged period. This defect cannot be explained by lack of antiinflammatory cytokines, such as interleukin 10 and transforming growth factor β. Instead, we have shown that a soluble activity derived from endothelia and dependent on STAT3 is critical for suppression of interferon γ. These data define STAT3 signaling within endothelia as a critical antiinflammatory mediator and provide new insight to the protective function of ECs in inflammation.
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              Hormonal induction of endometrial receptivity.

              To review and synthesize information from the scientific literature pertaining to the hormonal induction of endometrial receptivity before ET. Critical review of selected scientific literature, synthesis and formulation of opinion. Not applicable. Prospective recipients of oocyte donation or candidates for frozen embryo transfer. Hormonal treatment for the purpose of induction of endometrial receptivity. Successful induction of endometrial receptivity, as substantiated by live birth rates, pregnancy rates, implantation rates or by measuring putative markers of endometrial receptivity. The practice of assisted reproductive technology, particularly third-party parenting, in which the source of oocytes is separated from the endometrium, has allowed a separate assessment of embryo and endometrial development. Endometrial receptivity can be induced by exogenously administered E(2) and P in a variety of regimens. The degree of synchrony between embryo and endometrium influences the probability of embryo implantation and may be controlled by initiating P stimulation at different times relative to the stage of embryo development. Many substances have been investigated as adjuncts to E(2) and P in the induction of endometrial receptivity, but at the present time, their value is unproven. Estrogen and P are the only hormones necessary to prepare the endometrium for implantation. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Indian J Med Res
                Indian J. Med. Res
                IJMR
                The Indian Journal of Medical Research
                Medknow Publications & Media Pvt Ltd (India )
                0971-5916
                0975-9174
                November 2014
                : 140
                : Suppl 1
                : S130-S136
                Affiliations
                [1] Department of Physiology, All India Institute of Medical Sciences, New Delhi, India
                [* ] Department of Physiology, North DMC Medical College, Hindu Rao Hospital, Delhi, India
                Author notes
                Reprint requests: Dr D. Ghosh, Department of Physiology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110 029, India e-mail: debabrata.ghosh1@ 123456gmail.com
                Article
                IJMR-140-130
                4345744
                25673534
                e089c671-4e15-4274-ab46-b08a3f1fad4a
                Copyright: © Indian Journal of Medical Research

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 22 January 2013
                Categories
                Review Article

                Medicine
                endometrium,mifepristone,receptivity,rhesus monkey,transcriptomics
                Medicine
                endometrium, mifepristone, receptivity, rhesus monkey, transcriptomics

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