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6 March 2018 Evaluation of PAI-1 in endometriosis using a homologous immunocompetent mouse model
Anna Buigues, Hortensia Ferrero, Jessica Martínez, Nuria Pellicer, Antonio Pellicer, Raúl Gómez
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Abstract

To analyze the role of PAI-1 (plasminogen activator inhibitor 1) in endometriotic lesion growth, we studied the effect of PAI-1 inhibition by PAI-039 using a homologous mousemodel of endometriosis that allows noninvasive monitoring. Endometrial tissue from donor mice was collected, labeled with mCherry adenovirus, and implanted into a subcutaneous pocket on the ventral abdomen of recipient mice. Seven days after transplantation, mice were randomly allocated in two groups and treated once daily for 2 weeks with either vehicle (control group) or PAI-1 inhibitor (PAI-039 group). Endometriotic lesion size generated in recipient mice was monitored by mCherry signal. Animals were euthanized 21 days after endometrial tissue implantation and endometriotic lesions were harvested for fibrin deposit and vascularization analyses. Collagen content was also examined to determine the overall effects of proteolysis on extracellular matrix degradation. We demonstrated that endometriotic lesions generated in recipient mice from both groups presented characteristics typical of human endometriotic lesions. We observed a significant decrease in fluorescence signal in endometriotic lesions from the PAI-039 group at the beginning of the treatment correlated with a decrease in endometriotic lesion size. PAI-1 inhibition significantly decreased lesion cell proliferation. In addition, endometriotic lesions from the PAI-1 inhibition group showed a decreased percentage of neovascularization as well as fibrin deposits. However, the density and distribution of collagen were not affected by PAI-039. Our results suggest that in vivo inhibition of PAI-1 by PAI-039 may be a useful strategy to reduce endometriotic lesion size by blocking angiogenesis.

Summary Sentence

PAI-1 inhibition reduces angiogenesis and decreases endometriotic lesion size in a homologous mouse model of endometriosis.

© The Author(s) 2018. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com
Anna Buigues, Hortensia Ferrero, Jessica Martínez, Nuria Pellicer, Antonio Pellicer, and Raúl Gómez "Evaluation of PAI-1 in endometriosis using a homologous immunocompetent mouse model ," Biology of Reproduction 99(2), 326-335, (6 March 2018). https://doi.org/10.1093/biolre/ioy057
Received: 14 November 2017; Accepted: 2 March 2018; Published: 6 March 2018
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