Leiomyoma Simultaneously Impair Endometrial BMP-2-Mediated Decidualization and Anticoagulant Expression through Secretion of TGF-β3

Sinclair, Donna; Mastroyannis, Alex; Taylor, Hugh S.

doi:10.1210/jc.2010-1450

Cited by 126 publications

(142 citation statements)

References 43 publications

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“…Intermenstrual bleeding is more likely related to endometrial instability (30) than to mechanical interference of leiomyomas; therefore, it is possible that women with higher PR expression in the leiomyoma and myometrium also have higher PR signaling in the endometrium and this is the main protective factor against irregular bleeding. Another possible mechanism is via paracrine communication from leiomyoma cells to endometrial stromal cells (31), but this is a complex network involving several growth factors with balanced activity on endometrial thickness and blood coagulation factors, and the net effect of progesterone is unknown. It is interesting that uterine bleeding is reduced by treatment with selective PR modulators through several putative mechanisms such as decreasing uterine blood flow and tumor volume, which may compensate for their progesterone antagonism in the endometrium (16,17).…”

Section: Discussionmentioning

confidence: 99%

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

Tsigkou

Reis

Lee

et al. 2015

Fertility and Sterility

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Section: Discussionmentioning

confidence: 99%

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

Tsigkou

Reis

Lee

et al. 2015

Fertility and Sterility

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“…This global effect of the myoma on endometrium suggests the presence of a diffusible factor that would influence endometrial receptivity remote from the myoma itself. Indeed, we have recently reported that TGFb secreted by myomas leads to decreased BMP receptor expression and subsequent HOXA10 repression (Sinclair et al 2011). Leiomyoma alter endometrial receptivity by secreting TGFb and altering genes including HOXA10 that are required for implantation.…”

Section: Hox Genes and Leiomyomamentioning

confidence: 97%

“…HOXA10 is expressed in human myometrium and its expression also has a menstrual cycledependent pattern. In vitro, HOXA10 expression is induced in endometrial stromal cells by progesterone, but in the primary myometrial cells, progesterone suppresses HOXA10 expression (Cermik et al 2001;Matsuzaki et al 2009;Rackow and Taylor 2010;Sinclair et al 2011). It is clear that there are different factors involved in the regulation of HOXA10 by progesterone in myometrium than endometrium.…”

Section: Hox Genes and Leiomyomamentioning

confidence: 99%

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

Taylor

2015

Cold Spring Harb Perspect Med

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201

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HOX genes convey positional identity that leads to the proper partitioning and adult identity of the female reproductive track. Abnormalities in reproductive tract development can be caused by HOX gene mutations or altered HOX gene expression. Diethylstilbestrol (DES) and other endocrine disruptors cause Mü llerian defects by changing HOX gene expression. HOX genes are also essential regulators of adult endometrial development. Regulated HOXA10 and HOXA11 expression is necessary for endometrial receptivity; decreased HOXA10 or HOXA11 expression leads to decreased implantation rates. Alternation of HOXA10 and HOXA11 expression has been identified as a mechanism of the decreased implantation associated with endometriosis, polycystic ovarian syndrome, leiomyoma, polyps, adenomyosis, and hydrosalpinx. Alteration of HOX gene expression causes both uterine developmental abnormalities and impaired adult endometrial development that prevent implantation and lead to female infertility.

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“…It has been demonstrated that progesterone (alone or in combination with 17β-estradiol) enhances the expression of CS/HSPG serglycin and DS/CSPG biglycan and versican in endometrial endothelial cells (8). Another potential regulator of endometrial PG synthesis is TGF-β3, which is capable of suppressing HSPG expression in endometrial stromal fibroblasts (9).…”

Section: Pgs In Human Endometriummentioning

confidence: 99%

Diverse functions of uterine proteoglycans in human reproduction (Review)

Kitaya¹,

Tada²,

Hayashi³

et al. 2012

Mol Med Report

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Abstract. Proteoglycans (PGs) are a group of heavily glycosylated proteins that are present throughout the mammalian body and are involved in a wide variety of biological phenomena, including structural maintenance, tissue remodeling, molecular presentation, cell adhesion and signal transmission. Previous studies have revealed an increasing number of roles for PGs in human reproduction. Several PGs are currently utilized or regarded as biomarkers for the diagnosis of certain pathological uterine conditions associated with infertility and obstetrical complications. The aim of this review was to discuss the involvement of PGs in the human uterus in reproductive biology and pathophysiology. Contents1. Introduction 2. PGs in human endometrium 3. Close association between miscarriage and deficiency in thrombomodulin and syndecan-4 4. Syndecan-1 as a diagnostic biomarker for plasmacyte infiltrates in chronic endometritis 5. DSPGs mediate ectopic growth and development of endometriosis 6. PGs in human myometrium and cervix 7. Contribution of fibromodulin, versican and decorin to structural maintenance and growth of uterine fibroids 8. Low myometrial syndecan-3 expression in dystocia 9. PGs in human placenta 10. Amniotic fluid perlecan and agrin as potential biomarkers for premature rupture of fetal membranes 11. Preventive role of syndecan-1 against pre-eclampsia 12. Upregulation of perlecan in the villi of gestational diabetes mellitus 13. Elevated amniotic fluid lumican concentration in fetus with Turner syndrome 14. Conclusions IntroductionProteoglycans (PGs) are a group of macromolecules which consist of one core protein and one or more covalently attached sulfated glycosaminoglycan (GAG) side chain(s). The PG core proteins are encoded by distinct genes and contain multiple functional domains that bind to and modulate a wide range of molecules, including chemokines, cytokines, growth factors, extracellular matrix (ECM) proteins, coagulation factors and lipid-metabolizing enzymes. The localization of PGs is attributed to the molecular and structural characteristics of their core proteins. GAGs consist of diversely epimerized/sulfated unbranched polysaccharide chains composed of 1,4-linked repeated disaccharide units. According to the combination of disaccharides, the sulfated GAG side chains are classified as chondroitin sulfate (CS), dermatan sulfate (DS), heparan sulfate (HS) and keratan sulfate (KS). The sulfation status of the GAG side chains in PGs varies with tissue type, location and age, which provides PGs with organ-dependent properties in molecular weight, structure and function (1).PGs are classified into two distinct types by their location in tissues: i) cell surface PGs and ii) ECM PGs (Table I). The cell surface PGs include the syndecan and glypican families. Syndecans are a group of transmembrane HSPGs that interact with and regulate various soluble molecules. Glypicans are glycosylphosphatidylinositol-anchored HSPGs on the outer surface of the plasma membrane that regulate multiple intracellular sig...

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Leiomyoma Simultaneously Impair Endometrial BMP-2-Mediated Decidualization and Anticoagulant Expression through Secretion of TGF-β3

Cited by 126 publications

References 43 publications

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

Increased progesterone receptor expression in uterine leiomyoma: correlation with age, number of leiomyomas, and clinical symptoms

The Role ofHoxGenes in Female Reproductive Tract Development, Adult Function, and Fertility

Diverse functions of uterine proteoglycans in human reproduction (Review)

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