scholarly journals Uterine epithelial cell proliferation and endometrial hyperplasia: evidence from a mouse model

2014 ◽  
Vol 20 (8) ◽  
pp. 776-786 ◽  
Author(s):  
Y. Gao ◽  
S. Li ◽  
Q. Li
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Mouse Model ◽  
Endometrial Hyperplasia ◽  
Epithelial Cell Proliferation ◽  
Uterine Epithelial Cell

412. The role of macrophages in regulating uterine epithelial cell proliferation

2008 ◽  
Vol 20 (9) ◽  
pp. 92
Author(s):  
A. S. Care ◽  
W. V. Ingman ◽  
M. J. Jasper ◽  
SA Robertson
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Epithelial Cells ◽  
Diphtheria Toxin ◽  
Functional Markers ◽  
Epithelial Cell Proliferation ◽  
Uterine Epithelial Cells ◽  
Uterine Epithelial Cell ◽  
Macrophage Depletion ◽  
Embryo Attachment

During the oestrous cycle, uterine epithelial cells respond to ovarian steroid hormones by producing an array of cytokines and chemokines that cause macrophage recruitment into the uterus and regulate macrophage activation phenotype. In turn, growth factors and cytokines synthesised by macrophages potentially impact epithelial cell proliferation, secretory function and receptivity to embryo attachment. To investigate the hypothesis that uterine macrophages are essential contributors to the proliferation of uterine epithelial cells, we have used an ovariectomy and steroid replacement model in CD11b-DTR ‘Mac-terminator' mice. These mice are engineered for CD11b promoter-driven expression of the monkey diphtheria toxin (DT) receptor, allowing acute systemic ablation of macrophages by administration of human diphtheria toxin (DT). CD11b-DTR mice were ovariectomised, then 2–4 weeks later were primed with E 2, followed by administration of DT (25 ng/g, ip) to effect macrophage depletion, and BrDU to label proliferating cells. Control mice were given PBS instead of DT. Uterine tissues were stained with F4/80 to detect macrophages, and anti-BrDU to detect BrDU+ epithelial cell nuclei. DT treatment was associated with a depletion of >90% of F4/80+ uterine macrophages. However, the numbers of BrDU+ epithelial cells and the architecture of the luminal epithelial surface and abundance of epithelial glands were similar in control and DT-treated uterine tissues. These data suggest that resident macrophages may not be essential for oestrogen-driven uterine epithelial cell proliferation. In ongoing experiments we are assessing the effect of macrophage depletion on epithelial cell expression of functional markers including those involved in regulation of embryo attachment.

Steviol retards renal cyst growth through reduction of CFTR expression and inhibition of epithelial cell proliferation in a mouse model of polycystic kidney disease

2014 ◽  
Vol 88 (3) ◽  
pp. 412-421 ◽  
Author(s):  
Chaowalit Yuajit ◽  
Chatchai Muanprasat ◽  
Anna-Rachel Gallagher ◽  
Sorin V. Fedeles ◽  
Suticha Kittayaruksakul ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Kidney Disease ◽  
Epithelial Cell ◽  
Mouse Model ◽  
Polycystic Kidney Disease ◽  
Renal Cyst ◽  
Epithelial Cell Proliferation ◽  
Polycystic Kidney ◽  
Cyst Growth

scholarly journals Progesterone Inhibits the Estrogen-Induced Phosphoinositide 3-Kinase→AKT→GSK-3β→Cyclin D1→pRB Pathway to Block Uterine Epithelial Cell Proliferation

2005 ◽  
Vol 19 (8) ◽  
pp. 1978-1990 ◽  
Author(s):  
Bo Chen ◽  
Haiyan Pan ◽  
Liyin Zhu ◽  
Yan Deng ◽  
Jeffrey W. Pollard
Keyword(s):  
Cell Cycle ◽  
Cell Proliferation ◽  
Epithelial Cell ◽  
Cyclin D1 ◽  
Nuclear Accumulation ◽  
Nuclear Antigen ◽  
Epithelial Cell Proliferation ◽  
Uterine Epithelial Cell ◽  
Gsk 3Β ◽  
Phosphoinositide 3 Kinase

Abstract The mammalian cell cycle is regulated by the cyclin/cyclin-dependent kinase (CDK) phosphorylation of the retinoblastoma (pRB) family of proteins. Cyclin D1 with its CDK4/6 partners initiates the cell cycle and acts as the link between extracellular signals and the cell cycle machinery. Estradiol-17β (E2) stimulates uterine epithelial cell proliferation, a process that is completely inhibited by pretreatment with progesterone (P4). Previously, we identified cyclin D1 localization as a key point of regulation in these cells with E2 causing its nuclear accumulation and P4 retaining it in the cytoplasm with the resultant inhibition of pRB phosphorylation. Here we show that E2 stimulates phosphoinositide 3-kinase to activate phosphokinase B/AKT to effect an inhibitory phosphorylation of glycogen synthase kinase (GSK-3β). This pathway is suppressed by P4. Inhibition of the GSK-3β activity in P4-treated uteri by the specific inhibitor, LiCl, reversed the nuclear accumulation of cyclin D1 and in doing so, caused pRB phosphorylation and the induction of downstream genes, proliferating cell nuclear antigen and Ki67. Conversely, inhibition of phosphoinositide 3 kinase by LY294002 or Wortmanin reversed the E2-induced GSK-3β Ser9 inhibitory phosphorylation and blocked nuclear accumulation of cyclin D1. These data show the reciprocal actions of E2 and P4 on the phosphoinositide 3-kinase through to the GSK-3β pathway that in turn regulates cyclin D1 localization and cell cycle progression. These data reveal a novel signaling pathway that links E2 and P4 action to growth factor-mediated signaling in the uterus.

scholarly journals Uterine ALK3 is essential during the window of implantation

2015 ◽  
Vol 113 (3) ◽  
pp. E387-E395 ◽  
Author(s):  
Diana Monsivais ◽  
Caterina Clementi ◽  
Jia Peng ◽  
Mary M. Titus ◽  
James P. Barrish ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Epithelial Cell ◽  
Signaling Pathways ◽  
Transforming Growth Factor ◽  
Apical Cell ◽  
Uterine Epithelium ◽  
Conditional Knockout ◽  
Epithelial Cell Proliferation ◽  
Uterine Receptivity ◽  
Uterine Epithelial Cell

The window of implantation is defined by the inhibition of uterine epithelial proliferation, structural epithelial cell remodeling, and attenuated estrogen (E2) response. These changes occur via paracrine signaling between the uterine epithelium and stroma. Because implantation defects are a major cause of infertility in women, identifying these signaling pathways will improve infertility interventions. Bone morphogenetic proteins (BMPs) are TGF-β family members that regulate the postimplantation and midgestation stages of pregnancy. In this study, we discovered that signaling via activin-like kinase 3 (ALK3/BMPR1A), a BMP type 1 receptor, is necessary for blastocyst attachment. Conditional knockout (cKO) of ALK3 in the uterus was obtained by producing Alk3flox/flox-Pgr-cre–positive females. Alk3 cKO mice are sterile and have defects in the luminal uterine epithelium, including increased microvilli density and maintenance of apical cell polarity. Moreover, Alk3 cKO mice exhibit an elevated uterine E2 response and unopposed epithelial cell proliferation during the window of implantation. We determined that dual transcriptional regulation of Kruppel-like factor 15 (Klf15), by both the transforming growth factor β (TGF-β) transcription factor SMAD family member 4 (SMAD4) and progesterone receptor (PR), is necessary to inhibit uterine epithelial cell proliferation, a key step for embryo implantation. Our findings present a convergence of BMP and steroid hormone signaling pathways in the regulation of uterine receptivity.

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