Human chorionic gonadotropin controls luteal vascular permeability via vascular endothelial growth factor by down regulation of a cascade of adhesion proteins

Junctional proteins regulate vascular permeability in the human corpus luteum. We demonstrate that vascular endothelial cadherin, nectin 2, and claudin 5 are involved in this regulation in a mutually interacting manner.

Daniel Herr, M.D., Hamish M. Fraser, Prof. Dr., Regina Konrad, B.S., Iris Holzheu, B.S., Rolf Kreienberg, Prof. Dr., Christine Wulff, Prof. Dr.

Volume 99, Issue 6, Pages 1749-1758.e6, May 2013


To study the functional interactions of junctional proteins acting as regulators of vascular permeability in the human corpus luteum. Here we investigated the role of VE-Cadherin, Nectin 2, and Claudin 5 as controllers of vascular endothelial cell permeability.

Performing immunhistochemical dual staining we co-localised the above mentioned proteins in the human corpus luteum.

Main outcome measures:
Using a granulosa-endothelial co-culture system, we revealed that hCG-treatment downregulates VE-Cadherin, Nectin 2, and Claudin 5 in endothelial cells via VEGFA.

Furthermore, the interaction of VE-Cadherin, Nectin 2, and Claudin 5 was investigated by silencing these proteins performing siRNA-knockdown. Interestingly, knockdown of VE15 Cadherin and Claudin 5 induced a decrease of the respective other protein. This downregulation was associated with changed rates of vascular permeability: hCG-induced a VEGFA-dependent downregulation of VE-Cadherin, Nectin 2, and Claudin 5 which increased the endothelial permeability in the co-culture system. Furthermore, knockdown of VE19 Cadherin, Nectin-2, and Claudin 5 also resulted in a consecutive increase of endothelial permeability for each different protein.

These results demonstrate for the first time that VE-cadherin, nectin 2, and claudin 5 are involved in the regulation of vascular permeability in a mutually interacting manner, which indicates their prominent role for the functionality of the human corpus luteum.

  • Micah Hill

    Congratulations on your interesting work! I found the cell culture model you used very interesting and I would imagine culture models for the corpus luteum are a challenge and that this would be challenging to study in vivo in humans. I was curious if you had animal model studies planned to further investigate this?

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