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Hamburg, Germany

Gellersen B.,Endokrinologikum Hamburg | Brosens J.J.,University of Warwick
Endocrine Reviews | Year: 2014

Decidualization denotes the transformation of endometrial stromal fibroblasts into specialized secretory decidual cells that provide a nutritive and immunoprivileged matrix essential for embryo implantation and placental development. In contrast to most mammals, decidualization of the human endometrium does not require embryo implantation. Instead, this process is driven by the postovulatory rise in progesterone levels and increasing local cAMP production. In response to falling progesterone levels, spontaneous decidualization causes menstrual shedding and cyclic regeneration of the endometrium. A growing body of evidence indicates that the shift from embryonic to maternal control of the decidual process represents a pivotal evolutionary adaptation to the challenge posed by invasive and chromosomally diverse human embryos. This concept is predicated on the ability of decidualizing stromal cells to respond to individual embryos in a manner that either promotes implantation and further development or facilitates early rejection. Furthermore, menstruation and cyclic regeneration involves stem cell recruitmentandrenders the endometrium intrinsically capable of adapting its decidual response to maximize reproductive success. Herewereview the endocrine, paracrine, and autocrine cues that tightly govern this differentiation process. In response to activation of various signaling pathways and genome-wide chromatin remodeling, evolutionarily conserved transcriptional factors gain access to the decidua-specific regulatory circuitry. Once initiated, the decidual process is poised to transit through distinct phenotypic phases that underpin endometrial receptivity, embryo selection, and, ultimately, resolution of pregnancy. Wediscusshowdisorders that subvert theprogramming, initiation, or progression of decidualization compromise reproductive health and predispose for pregnancy failure. © 2014 by the Endocrine Society. Source


Weimar C.H.E.,University Utrecht | Macklon N.S.,University Utrecht | Macklon N.S.,University of Southampton | Post Uiterweer E.D.,University Utrecht | And 2 more authors.
Human Reproduction Update | Year: 2013

background: Mechanisms underlying early reproductive loss in the human are beginning to be elucidated. The migratory and invasive capacity of human endometrial stromal cells (ESCs) is increasingly recognized to contribute to the intense tissue remodelling associated with embryo implantation, trophoblast invasion and endometrial regeneration. In this review, we examine the signals and mechanisms that control ESC migration and invasion and assess how deregulation of these cell functions contributes to common reproductive disorders. methods: The PubMed database was searched for publications on motility and invasiveness of human ESCs in normal endometrial function and in reproductive disorders including implantation failure, recurrent pregnancy loss (RPL), endometriosis and adenomyosis, covering the period 2000-2012. results: Increasing evidence suggests that implantation failure and RPLinvolve abnormal migratory responses of decidualizing ESCsto embryo and trophoblast signals. Numerous reports indicate that endometriosis, as well as adenomyosis, is associated with increased basal and stimulated invasiveness of ESCs and their progenitor cells, suggesting a link between a heightened menstrual repair response and the formation of ectopic implants. Migration and invasiveness of ESCs are controlled by a complex array of hormones, growth factors, chemokines and inflammatory mediators, and involve signalling through Rho GTPases, phosphatidylinositol-3-kinase and mitogen-activated protein kinase pathways.conclusions: Novel concepts are extending our understanding of the key functions of ESCs in effecting tissue repair imposed by cyclic menstruation and parturition. Migration of decidualizing ESCs also serves to support blastocyst implantation and embryo selection through discriminate motile responses directed by embryo quality. Targeting regulatory molecules holds promise for developing new strategies for the treatment of reproductive disorders such as endometriosis and recurrent miscarriage; and harnessing the migratory capacity of progenitor mesenchymal stem cells in the endometrium may offer new opportunities in regenerative medicine. © The Author 2013. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. Source


Bartmann C.,University of Wurzburg | Segerer S.E.,Endokrinologikum Hamburg | Rieger L.,Hospital of Landshut Achdorf | Kapp M.,University of Wurzburg | And 2 more authors.
American Journal of Reproductive Immunology | Year: 2014

Problem: To date, a multiplicity of factors contributing to the establishment and progression of a successful pregnancy have been postulated. There is emerging evidence that decidual leukocytes could be decisive factors during pregnancy. Despite numerous investigations on immune cells in human early pregnancy decidua, little is known about the physiological composition and proportion of the various immune cell populations during the different phases of pregnancy. In this study, we therefore analyzed the proportion of the dominant decidual leukocytes in human tissue samples derived from all phases of pregnancy. Methods: Single cell suspensions were prepared from decidual samples from 205 patients at 6-40 weeks of gestation. Cell populations were analyzed by flow cytometry, and immune cell populations were quantified as percentage of decidual CD45+ cells. Results: There was generally no difference in immune cell counts comparing decidua of healthy gestations and those with systemic inflammation. Overall, the proportion of uNK cells continuously decreased, while the amount of monocytes, immature dendritic cells, and T cells increased until term. Striking modifications in cell counts were seen during the 7th week compared with the 6th and later weeks of gestation. Conclusion: Studying the proportion of decidual immune cells during pregnancy, we detected a unique pattern which could be useful to design novel therapies for pathological conditions during pregnancy. © 2013 John Wiley & Sons Ltd. Source


Weimar C.H.E.,University Utrecht | Kavelaars A.,University Utrecht | Brosens J.J.,University of Warwick | Gellersen B.,Endokrinologikum Hamburg | And 4 more authors.
PLoS ONE | Year: 2012

Background: The aetiology of recurrent miscarriage (RM) remains largely unexplained. Women with RM have a shorter time to pregnancy interval than normally fertile women, which may be due to more frequent implantation of non-viable embryos. We hypothesized that human endometrial stromal cells (H-EnSCs) of women with RM discriminate less effectively between high-and low-quality human embryos and migrate more readily towards trophoblast spheroids than H-EnSCs of normally fertile women. Methodology/Principal Findings: Monolayers of decidualized H-EnSCs were generated from endometrial biopsies of 6 women with RM and 6 fertile controls. Cell-free migration zones were created and the effect of the presence of a high-quality (day 5 blastocyst, n = 13), a low-quality (day 5 blastocyst with three pronuclei or underdeveloped embryo, n = 12) or AC-1M88 trophoblast cell line spheroid on H-ESC migratory activity was analyzed after 18 hours. In the absence of a spheroid or embryo, migration of H-EnSCs from fertile or RM women was similar. In the presence of a low-quality embryo in the zone, the migration of H-EnSCs of control women was inhibited compared to the basal migration in the absence of an embryo (P<0.05) and compared to the migration in the presence of high-quality embryo (p<0.01). Interestingly, the migratory response H-EnSCs of women with RM did not differ between high- and low-quality embryos. Furthermore, in the presence of a spheroid their migration was enhanced compared to the H-EnSCs of controls (p<0.001). Conclusions: H-EnSCs of fertile women discriminate between high- and low-quality embryos whereas H-EnSCs of women with RM fail to do so. H-EnSCs of RM women have a higher migratory response to trophoblast spheroids. Future studies will focus on the mechanisms by which low-quality embryos inhibit the migration of H-EnSCs and how this is deregulated in women with RM. © 2012 Weimar et al. Source


Jacobeit J.W.,Endokrinologikum Hamburg
Gynakologische Praxis | Year: 2014

The care of transsexual patients is a lifelong and honestly interdisciplinary task for health professionals. The knowledge of the diagnostic criteria and treatment guidelines is of enormous importance for the health professional. Transsexualism is not an issue of sexuality and not a disease in the traditional sense but rather a disorder of gender identity (gender dysphoria). Transsexual patients require multiprofessional medical and social assistance to enable them a suitable life in an appropriate quality. First of all, there is a need of diagnosis and psychotherapy of gender dysphoria by an experienced mental health professional. Prior cross sex hormonal treatment a written "Mental Health Professional's Documentation Letter for Hormone Therapy" is needed. Prior each hormone prescription a counselling and a screening for risk factors or accompanying diseases is recommended. Guidelines are published for the cross sex hormone treatment. The collaboration with a centre with well experienced health professionals or contact with Transgender teams for the treatment of transsexual patients is recommended. Transsexual patients require life-long multi-professional medical attention and care, and they will gratefully accept this offer. Source

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