The effect of hyperstimulation on transforming growth factor β1 and β2 in the rat uterus: possible consequences for embryo implantation

Jovanović, Aleksandra; Kramer, Beverley

doi:10.1016/j.fertnstert.2008.12.092

Cited by 14 publications

(12 citation statements)

References 82 publications

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“…Because estrogen and some growth factors regulate endometrial stem/progenitor cells, they may affect the microenvironment of the endometrial stem cells. Estrogen causes changes in ovarian steroids, leading to alterations in the endogenous hormonal environment, with the interruption of the endometrial environment necessary for effective embryo implantation due to the clear rise in TGF-β expression [ 43 ]. Rageh et al [ 44 ] showed that CTGF and TGF-β mRNA were powerfully stimulated after estradiol administration in ovariectomized mice.…”

Section: Discussionmentioning

confidence: 99%

Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model

et al. 2018

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BackgroundMesenchymal stem cells (MSCs) have diverse functions in regulating injury and inflammation through the secretion of extracellular vesicles (EVs).MethodsIn this study, we investigated the systemic administration of extracellular vesicles derived from human umbilical cord mesenchymal stem cells (UCMSCs-EVs) as a therapeutic agent for intrauterine adhesions (IUAs) caused by endometrial injury. Additionally, we investigated the therapeutic impact of both UCMSCs-EVs and estrogen either separately or in combination in a rat model. The inflammation, vascularization, proliferation, and extent of fibrosis were assessed by a histopathological and immunohistochemical assessment using transforming growth factor (TGF)-β as a fibrotic marker and vascular endothelial growth factor (VEGF) as a vascular marker. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6 (inflammatory cytokines), CD140b (a marker of endometrial stem cells), and RUNX2 (an antifibrotic factor). Finally, Western blotting was used to evaluate collagen I and β-actin expression.ResultsThe therapeutic groups treated with either UCMSCs-EVs alone or combined with estrogen exhibited a significant decrease in inflammation and fibrosis (TNF-α, TGF-β, IL-1, IL-6, RUNX2, and collagen-I) as well as a significant decrease in vascularization (VEGF) compared with the untreated rats with IUAs. The most significant results were obtained in animals with IUAs that received a combined therapy of UCMSCs-EVs and estrogen.ConclusionsWe conclude that the synergistic action of human UCMSCs-EVs combined with estrogen provides a highly effective alternative regenerative agent in IUA treatment.

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Section: Discussionmentioning

confidence: 99%

Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model

et al. 2018

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“…A recent study suggested that exosomes derived from human umbilical cord stem cells (hucMSCs) could ameliorate carbon tetrachloride (CCl 4 ) induced liver fibrosis through lowering of TGF-β gene expression [ 31 ]. Hyperstimulation with estrogen increases the expression of TGF-β [ 32 ]. Regarding CTGF, there was a statistical significant decrease in neupogen treated group and MSCs treated groups ( P -value <0.05) with greater significant decrease observed in MSCs and neupogen treated group and decreased fibrosis in histologically examined sections compared with fibrosis group.…”

Section: Discussionmentioning

confidence: 99%

Neupogen and mesenchymal stem cells are the novel therapeutic agents in regeneration of induced endometrial fibrosis in experimental rats

et al. 2017

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Endometrial fibrosis is the presence of intrauterine adhesions (IUAs) after any uterine surgery or curettage and it results in infertility and recurrent pregnancy loss. We evaluated the role of human mesenchymal stem cells (hMSCs) as a therapeutic agent of endometrial fibrosis. We also compared the effect of MSCs with the effect of estrogen and neupogen either each alone or as a combined therapy with MSCs. This experimental study was performed on 84 albino rats which were divided into seven groups (n=12 rats/group) as follows, group1: normal control rats, group 2: induced fibrosis, group 3: induced fibrosis that received oral estrogen, group 4: induced fibrosis that received hMSCs, group 5: induced fibrosis that received hMSCs and estrogen, group 6: induced fibrosis that received neupogen, and group 7: induced fibrosis that received hMSCs and neupogen. The extent of fibrosis, vascularization, and inflammation were evaluated by; qRT-PCR for interleukin 1 (IL-1), interleukin 6 (IL-6), TNF, vascular endothelial growth factor (VEGF), transforming growth factor-β (TGF-β), and RUNX; ELISA for connective tissue growth factor (CTGF); Western blotting for collagen-I; immunohistochemistry examination for VEGF and RUNX-2; and histopathological assessment. In therapeutic groups either by hMSCs alone or combined with estrogen or neupogen; fibrosis and inflammation (IL-1, IL-6, TNF, TGF-β, RUNX, CTGF, and collagen-I) were significantly decreased but vascularization (VEGF) was significantly increased (P<0.05) compared with induced fibrosis group. The most significant result was obtained in fibrosis that received combined therapy of hMSCs and neupogen (P=0.000). Stem cells and neupogen are a highly effective alternative regenerative agents in endometrial fibrosis.

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“…The basolateral localization of prominin-2 during OH pregnancy is similar to the distribution of prominin-2 seen in ovariectomized rats treated with estrogen and therefore may be caused by the supraphysiological level of estrogen that results from OH treatment. 49,52,60 Quantitative TEM analysis in this study revealed that the increase in morphological caveolae that occurs during normal pregnancy 18 is also disrupted by the OH procedure. The retention of prominin-2 in the basal plasma membrane during OH pregnancy is suggested to continue sequestering cholesterol in lipid rafts, thereby preventing formation of morphological caveolae.…”

Section: Ovarian Hyperstimulation Disrupts the Redistribution Of Prominin-2 And The Increase In Morphological Caveolaementioning

confidence: 64%

“…[46][47][48][49] Animal ovarian hyperstimulation (OH) models have been developed to examine this phenomenon and have demonstrated numerous abnormalities in the endometrium after OH treatment. [50][51][52] This study thus also investigates the potential impact of OH treatment on morphological caveolae and whether this may be related to prominin-2 and caveolin-1 abundance and localization.…”

Section: Introductionmentioning

confidence: 99%

Prominin-2 Prevents the Formation of Caveolae in Normal and Ovarian Hyperstimulated Pregnancy

et al. 2017

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During early pregnancy, uterine epithelial cells (UECs) become less adherent to the underlying basal lamina and are subsequently removed so the blastocyst can invade the underlying stroma. This process involves the removal of focal adhesions from the basal plasma membrane of UECs. These focal adhesions are thought to be internalized by caveolae, which significantly increase in abundance at the time of blastocyst implantation. A recent in vitro study indicated that prominin-2 prevents the formation of caveolae by sequestering membrane cholesterol. The present study examines whether prominin-2 affects the formation of caveolae and loss of focal adhesions in UECs during normal and ovarian hyperstimulation (OH) pregnancy in the rat. At the time of fertilization during normal pregnancy, prominin-2 is distributed throughout the basolateral plasma membrane. However, at the time of implantation and coincident with an increase in caveolae, prominin-2 is lost from the basal plasma membrane. In contrast, prominin-2 remains in the basolateral plasma membrane throughout OH pregnancy. Transmission electron microscopy showed that this membrane contained few caveolae throughout OH pregnancy. Our results indicate that prominin-2 prevents the formation of caveolae. We suggest the retention of prominin-2 in the basal plasma membrane during OH pregnancy prevents the formation of caveolae and is responsible for the retention of focal adhesions in this membrane, thereby contributing to the reduced implantation rate observed after such treatments.

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The effect of hyperstimulation on transforming growth factor β1 and β2 in the rat uterus: possible consequences for embryo implantation

Cited by 14 publications

References 82 publications

Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model

Human mesenchymal stem cell-derived extracellular vesicles/estrogen combined therapy safely ameliorates experimentally induced intrauterine adhesions in a female rat model

Neupogen and mesenchymal stem cells are the novel therapeutic agents in regeneration of induced endometrial fibrosis in experimental rats

Prominin-2 Prevents the Formation of Caveolae in Normal and Ovarian Hyperstimulated Pregnancy

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