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Biology of the endometrium
Published in Barry G. Wren, Progress in the Management of the Menopause, 2020
An increasing amount of evidence suggests that at least some of the actions of steroid hormones in the endometrium are mediated by growth factors and cytokines, which can act in a juxtacrine, paracrine or autocrine fashion (Figure 2)11. The list of growth factors and cytokines identified in human endometrium is growing all the time (Table 1)12–21. Each of the endometrial cell types may synthesize different growth factors/cytokines and each of them may mediate a specific steroid hormone-dependent function. Cytokines which modulate a variety of cellular functions in the endometrium have been comprehensively reviewed by Tabibzadeh21. Epidermal growth factor (EGF) is supposed to have a role in endometrial proliferation, differentiation and angiogenesis13. Glycodelin has immuno-suppressive and contraceptive activities15. Transforming growth factor (TGF) ß has a variety of actions; for example, it enhances the production of extracellular matrix components and up-regulates a variety of receptors that are important in mediating cell–cell and cell–extracellular matrix interactions19. Endothelin (ET)-1 is a potent vasoconstrictor12. Vascular endothelial cell growth factor (VEGF) is an angiogenic factor20. The insulin-like growth factor (IGF) system, including IGF-I and IGF-II, their receptors and soluble IGF-binding proteins (IGFBP), is perhaps the best characterized growth factor system in the endometrium and will be presented here as an example16.
Molecular basis and biomarkers of disease activity
Published in Seema Chopra, Endometriosis, 2020
Glycodelin A is a cell proliferation promotor that also promotes neovascularization. It also exhibits immunosuppressive properties and acts via inactivation of T and NK (natural killer) cells. Several studies have previously been conducted to explore the diagnostic utility of this marker for endometriosis; however, they have yielded conflicting results, with some suggesting a significant association of the elevated levels with endometriosis while the others indicating only a limited clinical utility [4,9].
Acquired uterine conditions, reproductive surgery, and recurrent implantation failure
Published in Efstratios M. Kolibianakis, Christos A. Venetis, Recurrent Implantation Failure, 2019
Dimitra Aivazi, Eleni Tsakalidou, Grigoris F. Grimbizis
Another alteration that may explain the effect of EP on implantation is the elevated levels of glycodelin, a glycoprotein that inhibits natural killer (NK) cell activity and sperm-oocyte binding. In normal ovulatory endometrium, low levels of glycodelin, six days before until five days after ovulation, permit fertilization followed by a rise in order to suppress NK cells and facilitate implantation. Elevated levels of glycodelin may modify endometrial receptivity when EP are present.53
Mucosal biomarkers for endometrial receptivity: A promising yet underexplored aspect of reproductive medicine
Published in Systems Biology in Reproductive Medicine, 2022
Mark Jain, Larisa Samokhodskaya, Elena Mladova, Olga Panina
Glycodelin is a secretory glycoprotein, which is primarily expressed in different parts of the male and female reproductive system (Uchida et al. 2013). Glycodelin is frequently referred to as placental protein 14 because of its initial discovery in amniotic fluid (Krivonosov et al. 1979). In humans, glycodelin is present in four glycoforms (glycodelin-A, -S, -F, -C), which are characterized by different functions, including various interactions with spermatozoa, endometrial epithelial cell adhesion toward embryos, and suppression of natural killer cytotoxicity (Uchida et al. 2013). The expression of glycodelin in endometrial tissue was found to be significantly upregulated during the peak estradiol and progesterone levels timed to luteinizing hormone (LH) surge – this exact timeframe is considered to be ‘the window of implantation’ by many researchers (Kao et al. 2002a).
Endometrium receptivity in premature ovarian insufficiency – how to improve fertility rate and predict diseases?
Published in Gynecological Endocrinology, 2018
Svetlana Vujović, Miomira Ivovic, Milina Tančić-Gajić, Ljiljana Marina, Aleksandar Ljubic, Svetlana Dragojević-Dikić, Andrea Ricardo Genazzani
Endometrial glycodelin expression is an important predictor of pregnancy outcomes. Glycodelin is a major gycoprotein induced by progesteron and secreted from the secretory and decidual endometrium during the luteal phase [29]. It has apoptotic and antiproliferative effects on T lymphocytes and immunosuppresive and inhibiting effects on NK cells. Glycodelin A protects embryo from maternal immune system during imlantation. Glycodelin induces apoptosis of monocytes before their differentiation into macrophages through mitochondrial pathway without affecting fagocytic activity. Low glycodelin is associated with growth retardation of endometrium and early embryo loss, as well as reccurent pregnancy loss. Hyperinsulinism and insulin resistance lowers circulating glycodelin. Metformin therapy increases glycodelin threefolds during the luteal phase [30]. Insulin like growth factor binding globulin 1 influences endometrium receptivity, as well. It facilitates adhesion process at the fetal-maternal interface during the periimplantation period and metformin increase IGFBP1 [31].
Do raised two-hour pre-pregnancy insulin levels confer the same risks of developing GDM, as raised fasting levels, in recurrent miscarriage patients?
Published in Journal of Obstetrics and Gynaecology, 2020
Catherine McCormack, Shalem Leemaqz, Denise Furness, Gustaaf Dekker, Claire T. Roberts
Jakubowicz et al. (2004) found that hyperinsulinaemia led to reduced concentrations of insulin-like growth factor binding protein-1 (IGFBP-1) and glycodelin in early pregnancy, thereby increasing the chance of miscarriages. Glycodelin is an immunomodulatory protein involved in implantation, and Glycodelin -A is found in abundant levels in the decidua in early pregnancy. It plays an important role both in placental development and fetomaternal defence. Abnormal levels are associated with unexplained infertility and recurrent pregnancy loss (Glueck et al. 2008). Interestingly, insulin can negatively regulate the concentrations of glycodelin and IGFBP-1, and this may be the mechanism by which it increases the risk of miscarriages.