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      Gene expression analysis of membrane progesterone receptors in women with recurrent spontaneous abortion: a case control study

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          Abstract

          Objective

          Recurrent spontaneous abortion (RSA) is a condition which is defined as three consecutive pregnancy losses prior to 20 weeks from the last menstrual period. Progesterone is a steroid hormone that has an essential role in the implantation and maintenance of pregnancy. The progesterone signaling is performed by nuclear progesterone receptors (NPRs) and membrane progesterone receptors (mPR). The aim of this study was to analyze gene expression of mPR- α, mPR- β and NPR in the endometrium of patients with a history of RSA compared to normal fertile women.

          Results

          In this study, endometrial samples were obtained from 10 women with a history of RSA and 10 fertile women during days 10–14 of menstrual cycle. Relative expression of mPR- α, mPR- β and NPR genes were studied by a quantitative real time polymerase chain reaction (qRT-PCR) and compared between the two groups. The mean relative expression of mPR- β gene was significantly lower in the case group compared to the fertile women (p < 0.05). However, the gene expression of mPR- α and NPR showed no significant difference between two groups. The findings suggest a reduction of endometrial gene expression of mPR- β in RSA patients may play an important role in pathogenesis of RSA.

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          Most cited references24

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          Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities.

          Although progesterone has been recognized as essential for the establishment and maintenance of pregnancy, this steroid hormone has been recently implicated to have a functional role in a number of other reproductive events. The physiological effects of progesterone are mediated by the progesterone receptor (PR), a member of the nuclear receptor superfamily of transcription factors. In most cases the PR is induced by estrogen, implying that many of the in vivo effects attributed to progesterone could also be the result of concomitantly administered estrogen. Therefore, to clearly define those physiological events that are specifically attributable to progesterone in vivo, we have generated a mouse model carrying a null mutation of the PR gene using embryonic stem cell/gene targeting techniques. Male and female embryos homozygous for the PR mutation developed normally to adulthood. However, the adult female PR mutant displayed significant defects in all reproductive tissues. These included an inability to ovulate, uterine hyperplasia and inflammation, severely limited mammary gland development, and an inability to exhibit sexual behavior. Collectively, these results provide direct support for progesterone's role as a pleiotropic coordinator of diverse reproductive events that together ensure species survival.
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            Progesterone signaling in human myometrium through two novel membrane G protein-coupled receptors: potential role in functional progesterone withdrawal at term.

            Progestin withdrawal is a crucial event for the onset of labor in many mammalian species. However, in humans the mechanism of a functional progestin withdrawal is unclear, because progestin concentrations do not drop in maternal plasma preceding labor. We report the presence of two novel functional membrane progestin receptors (mPRs), mPRalpha and mPRbeta, in human myometrium that are differentially modulated during labor and by steroids in vitro. The mPRs are coupled to inhibitory G proteins, resulting in a decline in cAMP levels and increased phosphorylation of myosin light chain, both of which facilitate myometrial contraction. Activation of mPRs leads to transactivation of PR-B, the first evidence for cross-talk between membrane and nuclear PRs. Progesterone activation of the mPRs leads also to a decrease of the steroid receptor coactivator 2. Our data indicate the presence of a novel signaling pathway mediated by mPRs that may result in a functional progestin withdrawal, shifting the balance from a quiescent state to one of contraction.
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              Systematic review and meta-analysis of genetic association studies in idiopathic recurrent spontaneous abortion.

              1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA.
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                Author and article information

                Contributors
                Reyhane.rahnama@yahoo.com
                Mitra_rafiee@yahoo.com
                saloomeh_fouladi@yahoo.com
                Maryamakbari_f@yahoo.com
                mehrabian@med.mui.ac.ir
                rezaei@med.mui.ac.ir
                Journal
                BMC Res Notes
                BMC Res Notes
                BMC Research Notes
                BioMed Central (London )
                1756-0500
                4 December 2019
                4 December 2019
                2019
                : 12
                : 790
                Affiliations
                [1 ]ISNI 0000 0001 1498 685X, GRID grid.411036.1, Department of Immunology, School of Medicine, , Isfahan University of Medical Sciences, ; Isfahan, Iran
                [2 ]ISNI 0000 0004 4911 7066, GRID grid.411746.1, Department of Nutrition, School of Public Health, , Iran University of Medical Sciences, ; Tehran, Iran
                [3 ]ISNI 0000 0001 1498 685X, GRID grid.411036.1, Department of Obstetrics and Gynecology, Al-Zahra Hospital, , Isfahan University of Medical Sciences, ; Isfahan, Iran
                Article
                4787
                10.1186/s13104-019-4787-x
                6894300
                31801604
                1bdca7b6-b726-458b-ad41-c1a302b42da6
                © The Author(s) 2019

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 22 August 2019
                : 5 November 2019
                Funding
                Funded by: Isfahan University of Medical Sciences.
                Award ID: 395057
                Award Recipient :
                Categories
                Research Note
                Custom metadata
                © The Author(s) 2019

                Medicine
                rsa,progesterone,mpr,endometrium,npr
                Medicine
                rsa, progesterone, mpr, endometrium, npr

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