Lysophosphatidic acid as a regulator of endometrial connective tissue growth factor and prostaglandin secretion during estrous cycle and endometrosis in the mare.
Abstract: Equine endometrosis is a chronic degenerative condition, described as endometrial fibrosis that forms in the stroma, under the basement membrane and around the endometrial glands. The role of lysophosphatidic acid (LPA) in the development of tissue fibrosis varies depending on the organ, and its profibrotic role in mare endometrosis remains unclear. The study aimed to establish the endometrial presence of LPA and its receptors (LPAR1-4), together with its effects on connective tissue growth factor (CTGF) and prostaglandins (PG) secretion from equine endometrium under physiological (estrous cycle), or pathological conditions (endometrosis). Mare endometria in the mid-luteal phase (n = 5 for each category I, IIA, IIB, III of Kenney and Doig) and in the follicular phase (n = 5 for each category I, IIA, III and n = 4 for IIB) were used. In experiment 1, the levels of LPA, LPAR1-4 mRNA level and protein abundance were investigated in endometria at different stages of endometrosis. In experiment 2, the in vitro effect of LPA (10 M) on the secretion of CTGF and PGs from endometrial tissue explants at different stages of endometrosis were determined. Results: Endometrial LPA concentration was higher in the mid-luteal phase compared to the follicular phase in category I endometrium (P < 0.01). There was an alteration in endometrial concentrations of LPA and LPAR1-4 protein abundance in the follicular phase at different stages of endometrosis (P < 0.05). Additionally, LPA increased the secretion of PGE from category I endometrium in both phases of the estrous cycle (P < 0.05). The effect of LPA on the secretion of CTGF and PGF from endometrial tissue was altered depending on different stages of endometrosis (P < 0.05). Conclusions: Our data indicate that endometrosis disturbs proper endometrial function and is associated with altered endometrial LPA concentration, its receptor expression and protein abundance, PGE/PGF ratio, and CTGF secretion in response to LPA. These changes could influence several physiological events occurring in endometrium in mare during estrous cycle and early pregnancy.
Publication Date: 2020-09-17 PubMed ID: 32943074PubMed Central: PMC7499873DOI: 10.1186/s12917-020-02562-6Google Scholar: Lookup
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Summary
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This research investigates the role of lysophosphatidic acid (LPA) in equine endometrosis, a chronic degenerative condition in horses. The study sought to determine the presence of LPA and its effects on endometrial growth in mares during their estrous cycle and in cases of endometrosis.
Objectives of the Research
- The objective of this study was to ascertain the presence of LPA and its receptors (LPAR1-4) in the equine endometrium during normal physiological conditions (estrous cycle) and pathological conditions (endometrosis).
- The research also aimed to investigate the effects of LPA on the secretion of Connective Tissue Growth Factor (CTGF) and prostaglandins (PG) from the equine endometrium in regular and pathological conditions.
Method and Experiment Design
- The study involved equine endometria collected in both the mid-luteal phase and the follicular phase. They were categorised according to their stages of endometrosis using the Kenney and Doig classification.
- In the first experiment, the researchers measured the levels of LPA, and the LPAR1-4 mRNA level and protein abundance in the endometria across the different endometrosis stages.
- The second experiment focused on determining the in-vitro effect of LPA concentration on the secretion of CTGF and PGs from endometrial tissue explants at different endometrosis stages.
Findings of the Research
- The study found that the endometrial LPA concentration was higher in the mid-luteal phase compared to the follicular phase in category I endometrium.
- Endometrial concentrations of LPA and LPAR1-4 protein abundance varied in the follicular phase at different stages of endometrosis.
- The study also observed that LPA increased the secretion of PGE from category I endometrium in both phases of the estrous cycle.
- The impact of LPA on the secretion of CTGF and PGF from endometrial tissue appeared to change depending on the different stages of endometrosis.
Conclusions of the Study
- The research concluded that endometrosis disrupts the proper functioning of the equine endometrium and is associated with altered endometrial LPA concentrations, its receptor expression and protein abundance, PGE/PGF ratio, and CTGF secretion in response to LPA.
- These changes can have significant effects on several physiological events occurring in the mare’s endometrium during the estrous cycle and early pregnancy periods.
Cite This Article
APA
Szóstek-Mioduchowska A, Leciejewska N, Zelmańska B, Staszkiewicz-Chodor J, Ferreira-Dias G, Skarzynski D.
(2020).
Lysophosphatidic acid as a regulator of endometrial connective tissue growth factor and prostaglandin secretion during estrous cycle and endometrosis in the mare.
BMC Vet Res, 16(1), 343.
https://doi.org/10.1186/s12917-020-02562-6 Publication
Researcher Affiliations
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Tuwima-st 10, 10-748, Olsztyn, Poland. a.szostek-mioduchowska@pan.olsztyn.pl.
- Department of Animal Physiology and Biochemistry and Biostructure, Faculty of Veterinary Medicine and Animal Science, Poznan University of Life Sciences, Poznan, Poland.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Tuwima-st 10, 10-748, Olsztyn, Poland.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Tuwima-st 10, 10-748, Olsztyn, Poland.
- CIISA, Centre for Interdisciplinary Research in Animal Health, Faculty of Veterinary Medicine, University of Lisbon, Lisbon, Portugal.
- Department of Reproductive Immunology and Pathology, Institute of Animal Reproduction and Food Research of Polish Academy of Sciences, Olsztyn, Tuwima-st 10, 10-748, Olsztyn, Poland.
MeSH Terms
- Animals
- Connective Tissue Growth Factor / metabolism
- Dinoprostone / metabolism
- Endometriosis / metabolism
- Endometriosis / veterinary
- Endometrium / metabolism
- Endometrium / pathology
- Estrous Cycle / metabolism
- Female
- Fibrosis
- Horse Diseases / metabolism
- Horse Diseases / pathology
- Horses
- Lysophospholipids / metabolism
- RNA, Messenger / metabolism
- Receptors, Lysophosphatidic Acid / metabolism
- Uterine Diseases / veterinary
Grant Funding
- MAESTRO No2011/02/A/NZ5/00338 / Narodowe Centrum Nauki
- 005/RID/2018/19 / Ministerstwo Nauki i Szkolnictwa Wyu017cszego
Conflict of Interest Statement
The authors have declared no competing interests.
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Citations
This article has been cited 4 times.- Zdrojkowski Ł, Jasiński T, Ferreira-Dias G, Pawliński B, Domino M. The Role of NF-κB in Endometrial Diseases in Humans and Animals: A Review. Int J Mol Sci 2023 Feb 2;24(3).
- Jasiński T, Zdrojkowski Ł, Ferreira-Dias G, Kautz E, Juszczuk-Kubiak E, Domino M. Molecular Mechanism of Equine Endometrosis: The NF-κB-Dependent Pathway Underlies the Ovarian Steroid Receptors' Dysfunction. Int J Mol Sci 2022 Jul 1;23(13).
- Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares. Animals (Basel) 2022 Mar 19;12(6).
- Piotrowska-Tomala KK, Szóstek-Mioduchowska A, Jonczyk AW, Drzewiecka EM, Wrobel MH, Hojo T, Ferreira-Dias G, Skarzynski DJ. The effect of lysophosphatidic acid on myometrial contractility and the mRNA transcription of its receptors in the myometrium at different stages of endometrosis in mares. BMC Vet Res 2024 Dec 19;20(1):571.
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