Endometriosis development in relation to hypoxia: a murine model study

Abstract Background Endometriosis, due to its ambiguous symptoms, still remains one of the most difficult female diseases to treat, with an average diagnosis time of 7-9 years. The changing level of hypoxia plays an important role in a healthy endometrium during menstruation and an elevated expressi...

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Main Authors: Marta Hoffmann-Młodzianowska (Author), Radosław B. Maksym (Author), Katarzyna Pucia (Author), Monika Kuciak (Author), Andrzej Mackiewicz (Author), Claudine Kieda (Author)
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Published: BMC, 2024-10-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Marta Hoffmann-Młodzianowska  |e author 
700 1 0 |a Radosław B. Maksym  |e author 
700 1 0 |a Katarzyna Pucia  |e author 
700 1 0 |a Monika Kuciak  |e author 
700 1 0 |a Andrzej Mackiewicz  |e author 
700 1 0 |a Claudine Kieda  |e author 
245 0 0 |a Endometriosis development in relation to hypoxia: a murine model study 
260 |b BMC,   |c 2024-10-01T00:00:00Z. 
500 |a 10.1186/s10020-024-00973-x 
500 |a 1528-3658 
520 |a Abstract Background Endometriosis, due to its ambiguous symptoms, still remains one of the most difficult female diseases to treat, with an average diagnosis time of 7-9 years. The changing level of hypoxia plays an important role in a healthy endometrium during menstruation and an elevated expression of the hypoxia-inducible factor 1-alpha (HIF-1α) has been demonstrated in ectopic endometria. HIF-1α mediates the induction of proangiogenic factors and the development of angiogenesis is a critical step in the establishment and pathogenesis of endometriosis. Although the inhibition of angiogenesis has been proposed as one of the actionable therapeutic modalities, vascular normalization and re-oxygenation may become a possible new approach for therapeutic intervention. Methods Our goal was to investigate whether a selected murine model of endometriosis would be suitable for future studies on new methods for treating endometriosis. Non-invasive, high-resolution ultrasound-monitored observation was selected as the preclinical approach to obtain imaging of the presence and volume of the endometriotic-like lesions. The EF5 (2-(2-Nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetamide) compound that selectively binds to reduced proteins in hypoxic cells was used for hypoxia detection. The expression of Pten and other crucial genes linking endometriosis and hypoxia were also assessed. Results Using EF5, a pentafluorinated derivative of the 2-nitroimidazole that is metabolically reduced by oxygen-inhibitable nitroreductase, we confirmed that hypoxia did develop in the selected model and was detected in uterine and ectopic endometriotic lesions. Moreover, the changes in oxygen tension also influenced the expression level of significant genes related to endometriosis, like Pten, Trp53, Hif1a, Epas1, and Vegfa. Their strong modulation evidenced here is indicative of model reliability. Using high-resolution ultrasound-based imaging, we present a non-invasive method of visualization that enables the detection and observation of lesion evolution throughout the duration of the experiment, which is fundamental for further preclinical studies and treatment evaluation. Conclusions The selected model and method of visualization appear to be suitable for the study of new treatment strategies based on hypoxia alleviation and blood flow restoration. 
546 |a EN 
690 |a Endometriosis 
690 |a Murine model of endometriosis 
690 |a Hypoxia 
690 |a PTEN 
690 |a EF5 
690 |a High-resolution ultrasound 
690 |a Therapeutics. Pharmacology 
690 |a RM1-950 
690 |a Biochemistry 
690 |a QD415-436 
655 7 |a article  |2 local 
786 0 |n Molecular Medicine, Vol 30, Iss 1, Pp 1-12 (2024) 
787 0 |n https://doi.org/10.1186/s10020-024-00973-x 
787 0 |n https://doaj.org/toc/1528-3658 
856 4 1 |u https://doaj.org/article/3aad4ab9968c4a7988f4afffeafd8b29  |z Connect to this object online.