Animal Reproduction (AR)
https://animal-reproduction.org/article/doi/10.1590/1984-3143-AR2024-0070
Animal Reproduction (AR)
Thematic Section: X International Symposium on Animal Biology of Reproduction (ISABR)

The path to fertility: Current approaches to mare endometritis and endometrosis

Graça ML Ferreira-Dias; Joana Alpoim-Moreira; Anna Szóstek-Mioduchowska; Maria Rosa Rebordão; Dariusz J. Skarzynski

http://dx.doi.org/10.1590/1984-3143-AR2024-0070 Anim Reprod, vol.21, n3, e20240070, 2024
PDF
Downloads: 0
Views: 126

Abstract

The path to fertility in the mare requires an understanding of the hormonal influences, the immune response, genetics, and epigenetic mechanisms involved not only in physiological reproductive processes, but also such pathologies as endometritis and endometrosis. Endometritis may lead to endometrosis establishment. In the presence of endometritis, neutrophils arrive at the mare endometrium, and form neutrophil extracellular traps. While NETosis plays pivotal roles, prolonged inflammation can lead to chronic endometritis, endometrosis, and fertility issues. Matrix metalloproteinases and epigenetic changes influence the course of endometrosis. Inhibitors of specific enzymes involved in NETosis and epigenetic inhibitors have shown potential in reducing pro-fibrotic effects. Collagen type III (COL3) has emerged as a putative biomarker, correlating with endometrosis and useful in fertility assessment. Thus, COL3 may offer a non-invasive diagnostic tool, as a complement to histopathological methods. Epigenetic modifications and miRNA expressions offer new avenues for therapeutic strategies, emphasizing the importance of understanding the cellular mechanisms at play in mare endometrial fibrosis.

Keywords

mare, endometritis, endometrosis, Neutrophil Extracellular Traps, epigenetics

References

Alpoim-Moreira J, Fernandes C, Pimenta J, Bliebernicht M, Rebordão MR, Castelo-Branco P, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G. Metallopeptidades 2 and 9 genes epigenetically modulate equine endometrial fibrosis. Front Vet Sci. 2022b;9:970003. http://doi.org/10.3389/fvets.2022.970003. PMid:36032279.

Alpoim-Moreira J, Fernandes C, Rebordão MR, Amaral A, Pinto-Bravo P, Bliebernicht M, Skarzynski DJ, Ferreira-Dias G. Collagens and DNA methyltransferases in mare endometrosis. Reprod Domest Anim. 2019;54(S3, Suppl 3):46-52. http://doi.org/10.1111/rda.13515. PMid:31512314.

Alpoim-Moreira J, Fernandes C, Rebordão MR, Costa AL, Bliebernicht M, Nunes T, Szóstek-Mioduchowska A, Skarzynski DJ, Ferreira-Dias G. Collagen type III as a possible blood biomarker of fibrosis in equine endometrium. Animals (Basel). 2022a;12(14):1854. http://doi.org/10.3390/ani12141854. PMid:35883401.

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;13(7):1212. http://doi.org/10.3390/ani13071212. PMid:37048467.

Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G. Inhibition of myeloperoxidase pro-fibrotic effect by noscapine in equine endometrium. Int J Mol Sci. 2023;24(4):3593. http://doi.org/10.3390/ijms24043593. PMid:36835008.

Amaral A, Fernandes C, Lukasik K, Szóstek-Mioduchowska A, Baclawska A, Rebordão MR, Aguiar-Silva J, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G. Elastase inhibition affects collagen transcription and prostaglandin secretion in mare endometrium during the estrous cycle. Reprod Domest Anim. 2018;53(Suppl 2):66-9. http://doi.org/10.1111/rda.13258. PMid:30238664.

Amaral A, Fernandes C, Morazzo S, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The inhibition of cathepsin G on endometrial explants with endometrosis in the mare. Front Vet Sci. 2020b;7:582211. http://doi.org/10.3389/fvets.2020.582211. PMid:33195599.

Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Gawronska-Kozak B, Telo da Gama L, Skarzynski DJ, Ferreira-Dias G. The In Vitro inhibitory effect of sivelestat on elastase induced collagen and metallopeptidase expression in equine endometrium. Animals (Basel). 2020a;10(5):863. http://doi.org/10.3390/ani10050863. PMid:32429399.

Amaral A, Fernandes C, Rebordão MR, Szóstek-Mioduchowska A, Lukasik K, Pinto-Bravo P, Telo da Gama L, Jan Skarzynski D, Ferreira-Dias G. Myeloperoxidase inhibition decreases the expression of collagen and metallopeptidase in mare endometria under in vitro conditions. Animals (Basel). 2021a;11(1):208. http://doi.org/10.3390/ani11010208. PMid:33467081.

Amaral A, Fernandes C, Szóstek-Mioduchowska A, Lukasik K, Rebordão MR, Pinto-Bravo P, Skarzynski DJ, Ferreira-Dias G. The inhibitory effect of noscapine on the in vitro cathepsin G-induced collagen expression in equine endometrium. Life (Basel). 2021c;11(10):1107. http://doi.org/10.3390/life11101107. PMid:34685478.

Amaral A, Fernandes C, Szóstek-Mioduchowska A, Rebordão MR, Skarzynski DJ, Ferreira-Dias G. Noscapine acts as a protease inhibitor of in vitro elastase-induced collagen deposition in equine endometrium. Int J Mol Sci. 2021b;22(10):5333. http://doi.org/10.3390/ijms22105333. PMid:34069423.

Brinkmann V, Reichard U, Goosmann C, Fauler B, Uhlemann Y, Weiss DS, Weinrauch Y, Zychlinsky A. Neutrophil extracellular traps kill bacteria. Science. 2004;303(5663):1532-5. http://doi.org/10.1126/science.1092385. PMid:15001782.

Katila T, Ferreira-Dias G. Evolution of the concepts of endometrosis, post breeding endometritis, and susceptibility of mares. Animals (Basel). 2022;12(6):779. http://doi.org/10.3390/ani12060779. PMid:35327176.

Kenney RM, Doig PA. Equine endometrial biopsy. In: Morrow, DA, editor. Current Therapy in Theriogenology 2: Diagnosis, treatment, and prevention of reproductive diseases in small and large animals. Philadelphia: WB Saunders; 1986. p. 723–729.

Rebordão MR, Amaral A, Fernandes C, Silva E, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Enzymes present in Neutrophil Extracellular Traps may stimulate the fibrogenic PGF2α pathway in the mare endometrium. Animals (Basel). 2021;11(9):2615. http://doi.org/10.3390/ani11092615. PMid:34573581.

Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Constituents of neutrophil extracellular traps induce in vitro collagen formation in mare endometrium. Theriogenology. 2018;113:8-18. http://doi.org/10.1016/j.theriogenology.2018.02.001. PMid:29452855.

Rebordão MR, Amaral A, Lukasik K, Szóstek-Mioduchowska A, Pinto-Bravo P, Galvão A, Skarzynski DJ, Ferreira-Dias G. Impairment of the antifibrotic prostaglandin E2 pathway may influence neutrophil extracellular traps-induced fibrosis in the mare endometrium. Domest Anim Endocrinol. 2019;67:1-10. http://doi.org/10.1016/j.domaniend.2018.10.004. PMid:30522057.

Rebordão MR, Carneiro C, Alexandre-Pires G, Brito P, Pereira C, Nunes T, Galvão A, Leitão A, Vilela C, Ferreira-Dias G. Neutrophil extracellular traps formation by bacteria causing endometritis in the mare. J Reprod Immunol. 2014;106:41-9. http://doi.org/10.1016/j.jri.2014.08.003. PMid:25218891.

Schoon HA, Schoon D, Klug E. Die endometriumbiopsie bei der stute im klinisch-gynäkologischen kontext. Pferdeheilkunde. 1997;13:453-64.

Szóstek AZ, Galvão AM, Hojo T, Okuda K, Skarzynski DJ. Interleukins affect equine endometrial cell function: modulatory action of ovarian steroids. Mediators Inflamm. 2014;2014:208103. http://doi.org/10.1155/2014/208103. PMid:24719522.

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. 2020a;10(1):1119. http://doi.org/10.1038/s41598-020-58109-0. PMid:31980722.

Szóstek-Mioduchowska A, Wójtowicz A, Sadowska A, Moza Jalali B, Słyszewska M, Łukasik K, Gurgul A, Szmatoła T, Bugno-Poniewierska M, Ferreira-Dias G, Skarzynski DJ. Transcriptomic profiling of mare endometrium at different stages of endometrosis. Sci Rep. 2023;13(1):16263. http://doi.org/10.1038/s41598-023-43359-5. PMid:37758834.

Szóstek-Mioduchowska AZ, Baclawska A, Okuda K, Skarzynski DJ. Effect of proinflammatory cytokines on endometrial collagen and metallopeptidase expression during the course of equine endometrosis. Cytokine. 2019b;123:154767. http://doi.org/10.1016/j.cyto.2019.154767. PMid:31265984.

Szóstek-Mioduchowska AZ, Baclawska A, Rebordão MR, Ferreira-Dias G, Skarzynski DJ. Prostaglandins effect on matrix metallopeptidases and collagen in mare endometrial fibroblasts. Theriogenology. 2020b;153:74-84. http://doi.org/10.1016/j.theriogenology.2020.04.040. PMid:32442743.

Szóstek-Mioduchowska AZ, Lukasik K, Skarzynski DJ, Okuda K. Effect of transforming growth factor -β1 on α-smooth muscle actin and collagen expression in equine endometrial fibroblasts. Theriogenology. 2019a;124:9-17. http://doi.org/10.1016/j.theriogenology.2018.10.005. PMid:30321755.

Wójtowicz A, Molcan T, Lukasik K, Żebrowska E, Pawlina-Tyszko K, Gurgul A, Szmatoła T, Bugno-Poniewierska M, Ferreira-Dias G, Skarzynski DJ, Szóstek-Mioduchowska A. The potential role of miRNAs and regulation of their expression in the development of mare endometrial fibrosis. Sci Rep. 2023;13(1):15938. http://doi.org/10.1038/s41598-023-42149-3. PMid:37743390.
 

Submitted date:
05/23/2024

Accepted date:
06/25/2024

66e02ef2a9539539d712d7bf animreprod Articles
Links & Downloads
1984-3143 (Electronic) 1806-9614 (Printed)
Anim Reprod ©2024 All rights reserved.

Anim Reprod

Share this page
Page Sections