Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.
Abstract: Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (+/-inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-beta1 and 11beta-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-beta1 and 11beta-HSD2 activities were significantly correlated to the severity of EPF (P<0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-beta1 resulting in myofibroblastic transformation. 11Beta-HSD2 in concert appears to modulate the severity of endometrial fibrosis.
Publication Date: 2006-01-09 PubMed ID: 16406651DOI: 10.1016/j.mce.2005.12.008Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The researchers conducted a study on equine endometrial fibrosis (EPF), a contributing factor to embryonic and fetal loss in mares. They found a strong correlation between the severity of EPF and the activities of angiotensin-converting enzyme (ACE), transforming growth factor-beta 1 (TGF-beta1), and 11beta-hydroxysteroid dehydrogenase type 2 (11β-HSD2).
Investigating Equine Endometrial Fibrosis
- The study focused on endometrial periglandular fibrosis (EPF), a condition in mares that affects conception and successful gestation. It is linked to embryonic and fetal loss.
- The researchers used the modified Kenney endometrial biopsy classification system to categorize the severity of EPF. This system classifies the severity of the condition from minimal (category I) to severe (category III), and also includes an inflammation indicator.
- To examine the condition, biopsy specimens were taken and stained. The researchers measured the endometrial ACE-binding activity, TGF-beta1, and 11beta-HSD2 activities in each.
Findings
- The study found significant ultrastructural changes in tissues from categories IIB and III, indicative of a myofibroblastic transformation. Myofibroblasts are cells that play a key role in wound healing and fibrosis.
- ACE-binding activity was found to be highest in tissues from category IIB of EPF. However, TGF-beta1 and 11beta-HSD2 activities were found to correlate with the severity of EPF, indicating that these factors increase as the condition becomes more severe.
Conclusions
- The researchers concluded that angiotensin II, generated locally, initiates the expression of TGF-beta1, thereby resulting in the transformation of cells into myofibroblasts.
- The study further suggests that 11Beta-HSD2 modulates the severity of endometrial fibrosis, thus presenting a potential target for treatment efforts.
The results of this study present new insights into the pathophysiology of equine endometrial fibrosis and potential avenues for therapeutic interventions.
Cite This Article
APA
Ganjam VK, Evans TJ.
(2006).
Equine endometrial fibrosis correlates with 11beta-HSD2, TGF-beta1 and ACE activities.
Mol Cell Endocrinol, 248(1-2), 104-108.
https://doi.org/10.1016/j.mce.2005.12.008 Publication
Researcher Affiliations
- Biomedical Sciences, W118 College of Veterinary Medicine, University of Missouri-Columbia, Columbia, MO 65211-0001, USA. ganjamv@missouri.edu
MeSH Terms
- 11-beta-Hydroxysteroid Dehydrogenase Type 2 / analysis
- Animals
- Endometrium / enzymology
- Endometrium / pathology
- Endometrium / ultrastructure
- Female
- Fibrosis
- Horse Diseases / diagnosis
- Horse Diseases / pathology
- Horses
- Peptidyl-Dipeptidase A / analysis
- Transforming Growth Factor beta / analysis
- Transforming Growth Factor beta1
- Uterine Diseases / diagnosis
- Uterine Diseases / pathology
- Uterine Diseases / veterinary
Citations
This article has been cited 7 times.- Wójtowicz A, Sadowska A, Molcan T, Słyszewska M, Drzewiecka EM, Tobolski D, Ferreira-Dias G, Szóstek-Mioduchowska A. Th1 and Th2 cells in equine endometrosis and their interactions with endometrial fibroblasts. Sci Rep 2025 Oct 16;15(1):36263.
- Amaral A, Sadowska A, Cerveira-Pinto M, Kordowitzki P, Skarzynski D, Ferreira-Dias G, Szóstek-Mioduchowska A. Ovarian steroids modulate mRNA expression of ECM associated genes and collagen deposition induced by TGF β1 in equine endometrium in vitro. Sci Rep 2025 Jan 2;15(1):538.
- Zhu Z, Huang Y, Song Y, Lu J, Hu L, Chen X. LncRNA MALAT1 Knockdown Alleviates Fibrogenic Response in Human Endometrial Stromal Cells Via the miR-22-3p/TGFβR1/Smad2/3 Pathway. Cell Biochem Biophys 2024 Dec;82(4):3573-3584.
- Alpoim-Moreira J, Szóstek-Mioduchowska A, Słyszewska M, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. 5-Aza-2'-Deoxycytidine (5-Aza-dC, Decitabine) Inhibits Collagen Type I and III Expression in TGF-β1-Treated Equine Endometrial Fibroblasts. Animals (Basel) 2023 Mar 30;13(7).
- Szóstek-Mioduchowska A, Słowińska M, Pacewicz J, Skarzynski DJ, Okuda K. Matrix metallopeptidase expression and modulation by transforming growth factor-β1 in equine endometrosis. Sci Rep 2020 Jan 24;10(1):1119.
- Guo LP, Chen LM, Chen F, Jiang NH, Sui L. Smad signaling coincides with epithelial-mesenchymal transition in a rat model of intrauterine adhesion. Am J Transl Res 2019;11(8):4726-4737.
- Costa MF, Carmona AK, Alves MF, Ryan TM, Davies HM, Anderson GA, Slocombe RF. Determination of angiotensin I-converting enzyme activity in equine blood: lack of agreement between methods of analysis. J Vet Sci 2011 Mar;12(1):21-5.
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