Molecular mechanisms of ovarian hyperstimulation syndrome: paracrine reduction of endothelial claudin 5 by hCG in vitro is associated with increased endothelial permeability

Rodewald, Miriam; Herr, D.; Duncan, W. Colin; Fraser, Hamish M.; G, Hack; Konrad, Regina; Gagsteiger, F.; Kreienberg, R.; Wulff, Christine

doi:10.1093/humrep/den479

Cited by 37 publications

(39 citation statements)

References 41 publications

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“…Therefore, an hCGdependent factor secreted by granulosa lutein cells was likely to be responsible, and this factor effecting endothelial cells is VEGF. Indeed, hCG stimulation of granulosa lutein cells increased VEGF protein production, as has been shown in previous papers (Neulen et al 1998, Fraser et al 2005, Rodewald et al 2009). In addition, hCG has been demonstrated to trigger VEGF expression in human luteal steroidogenic cells in vivo (Wulff et al 2001c).…”

Section: Cell Junctional Proteins and Permeabilitysupporting

confidence: 75%

“…It has been previously published that during simulated maternal recognition of pregnancy, there is a decrease in luteal endothelial Claudin 5 protein in the presence of hCG (Groten et al 2006). Moreover, a paracrine effect of hCG on endothelial Claudin 5, as well as on endothelial permeability, was observed in the presence of granulosa lutein cells (Rodewald et al 2009). The major effect of hCG on endothelial permeability and Claudin 5 expression remains indirect, occurring only in the presence of granulosa lutein cells.…”

Section: Cell Junctional Proteins and Permeabilitymentioning

confidence: 97%

“…It is most likely that the receptor has a hormone transcytosis function, meaning that the gonadotropin can be delivered through the endothelium to the target cell (Misrahi et al 1996). In order to investigate the cellular regulation of endothelial cells in the corpus luteum, an in vitro human cell co-culture representation was developed as a model for studying the effects of stimulatory agents on endothelial and granulosa lutein cells, as well as the molecular interactions between those cells (Rodewald et al 2009). It has been previously published that during simulated maternal recognition of pregnancy, there is a decrease in luteal endothelial Claudin 5 protein in the presence of hCG (Groten et al 2006).…”

Section: Cell Junctional Proteins and Permeabilitymentioning

confidence: 99%

“…In addition, hCG has been demonstrated to trigger VEGF expression in human luteal steroidogenic cells in vivo (Wulff et al 2001c). Increased levels of VEGF are capable of acting directly on neighboring endothelial cell (Rodewald et al 2009). The regulatory function of VEGF on endothelial cell permeability has previously been shown in cell culture experiments (Albert et al 2002, Villasante et al 2007.…”

Section: Cell Junctional Proteins and Permeabilitymentioning

confidence: 99%

“…In primates, if pregnancy does not occur, regression of the corpus luteum occurs 14 days after ovulation. However, in case of pregnancy, the survival of the corpus luteum is dependent on the effect of human chorionic gonadotropin (hCG) synthesized in the placenta (Matsubara et al 2000, Baird et al 2003, Duncan et al 2005, Del Canto et al 2007, Dickinson et al 2008, 2009). In the absence of pregnancy, maintenance of the mid-luteal corpus luteum can be achieved by administration of iatrogenic exogenous hCG (Illingworth & Heap 1971).…”

Section: Introductionmentioning

confidence: 99%

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Regulation of endothelial permeability in the primate corpora lutea: implications for ovarian hyperstimulation syndrome

Herr¹,

Bekes²,

Wulff³

2015

Reproduction

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In a developing human corpus luteum, a closely regulated cellular communication system exists between the luteal steroidogenic cells and endothelial cells. This system guaranties the vascularization process during luteal formation. The process is combined with rapid release of large amounts of progesterone into the bloodstream. The regulation of endothelial proliferation and permeability by LH and human chorionic gonadotropin (hCG) is integral to this process. On the cellular level, endothelial permeability is regulated by intercellular junctions, such as adherens junctions (AJ) and tight junctions (TJ), which act as zipper-like structures between interacting endothelial cells. Several cell junctional proteins are localized to the corpus luteum, including Occludin, Nectin 2, Claudin 1, and Claudin 5, as well as, vascular endothelial (VE)-Cadherin. It has been assumed that regulation of AJ-and TJ-proteins is of particular importance for permeability, and accordingly, for the functionality of the corpus luteum in early pregnancy, because treatment with hCG induces downregulation of juntional proteins in the luteal vessels. The effect of hCG on the adhesive molecules is mediated by VE growth factor (VEGF). On a functional level, the hCG-dependent and VEGF-mediated decrease in junctional proteins causes a decrease in the density of cell-cell closure and, accordingly, an increase in endothelial permeability. In doing so, the different junctional proteins are not only directly influenced by VEGF but also interact among themselves and influence each other reciprocally. Disturbances in this strictly, regulated interactions may explain the development of pathologies with increased vascular permeability, such as the ovarian hyperstimulation syndrome.Reproduction (2015) 149 R71-R79

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Section: Cell Junctional Proteins and Permeabilitysupporting

confidence: 75%

Section: Cell Junctional Proteins and Permeabilitymentioning

confidence: 97%

Section: Cell Junctional Proteins and Permeabilitymentioning

confidence: 99%

Section: Cell Junctional Proteins and Permeabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Regulation of endothelial permeability in the primate corpora lutea: implications for ovarian hyperstimulation syndrome

Herr¹,

Bekes²,

Wulff³

2015

Reproduction

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A palmtop‐sized microfluidic cell culture system driven by a miniaturized infusion pump

et al. 2012

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A palmtop-sized microfluidic cell culture system is presented. The system consists of a microfluidic device and a miniaturized infusion pump that possesses a reservoir of culture medium, an electrical control circuit, and an internal battery. The footprint of the system was downsized to 87 × 57 mm, which is, to the best of our knowledge, the smallest integrated cell culture system. Immortalized human microvascular endothelial cells (HMEC-1) and human umbilical vein endothelial cells (HUVEC) were cultured in the system. HMEC-1 in the system proliferated at the same speed as cells in a microchannel perfused by a syringe pump and cells in a culture flask. HUVEC in the system oriented along the direction of the fluid flow. Claudin-5, a tight junction protein, was localized along the peripheries of the HUVEC. We expect that the present system is applicable to various cell types as a stand-alone and easy-to-use system for microfluidic bioanalysis.

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Platelet‐derived growth factor BB and DD and angiopoietin1 are altered in follicular fluid from polycystic ovary syndrome patients

Scotti

Parborell

Irusta

et al. 2014

Molecular Reproduction Devel

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Polycystic ovary syndrome (PCOS) is the most common endocrinological pathology among women of reproductive age, and is characterized by abnormalities in ovarian angiogenesis, among other features. Consistent with this association, follicular fluid (FF) concentration and ovarian expression of vascular endothelial growth factor (VEGF) are increased in PCOS patients. In this study, we examined the protein levels of platelet-derived growth factor (PDGF) BB and DD (PDGFBB and PDGFDD), angiopoietin 1 and 2 (ANGPT1 and ANGPT2), and their soluble receptor sTIE2 in FF from PCOS and control patients undergoing assisted reproductive techniques. We also analyzed the effect of FF from PCOS and control patients on tight and adherens junction protein expression in an endothelial cell line. PDGFBB and PDGFDD were significantly lower whereas ANGPT1 concentration was significantly higher in FF from PCOS patients than from control patients. No changes were found in the concentration of ANGPT2 or sTIE2. Expression of claudin-5 was significantly increased in endothelial cells incubated for 24 hr in the presence of FF from PCOS versus from control patients, while vascular-endothelial cadherin, β-catenin, and zonula occludens 1 expression were unchanged. The changes observed in the levels of PDGF isoforms and ANGPT1 may prevent VEGF-induced vascular permeability in the PCOS ovary by regulating endothelial-cell-junction protein levels. Restoring the levels of angiogenic factors may provide new insights into PCOS treatment and the prevention of ovarian hyperstimulation syndrome in affected women.

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Molecular mechanisms of ovarian hyperstimulation syndrome: paracrine reduction of endothelial claudin 5 by hCG in vitro is associated with increased endothelial permeability

Abstract: For OHSS, this novel paradigm suggests that hCG can increase endothelial permeability by up-regulating VEGF in LGCs which causes reduction in endothelial claudin 5 expression.

Cited by 37 publications

References 41 publications

Regulation of endothelial permeability in the primate corpora lutea: implications for ovarian hyperstimulation syndrome

Regulation of endothelial permeability in the primate corpora lutea: implications for ovarian hyperstimulation syndrome

A palmtop‐sized microfluidic cell culture system driven by a miniaturized infusion pump

Platelet‐derived growth factor BB and DD and angiopoietin1 are altered in follicular fluid from polycystic ovary syndrome patients

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