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BMC veterinary research2024; 20(1); 571; doi: 10.1186/s12917-024-04384-2

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.

Abstract: Endometrosis (chronic degenerative endometritis) results in morphological changes in the equine endometrium and impairs its secretory function. However, the effect of this condition on the myometrium remains unclear. Lysophosphatidic acid (LPA) may affect female reproductive function and embryo transport by influencing uterine contractility through its receptors (LPARs). The objective of this study was to determine myometrial LPAR1-6 mRNA transcription, and the effects of LPA on myometrial contractions in mares with endometrosis during the mid-luteal and follicular phases of the estrous cycle. Results: A reduction in myometrial LPAR1 mRNA transcription was observed in mares with endometrosis during the mid-luteal phase, in comparison to those with category I endometria (P < 0.05). While, upregulation of myometrial LPAR3 or LPAR6 mRNA transcription was observed in mares with category III or IIB endometria; respectively (P < 0.05). An increase in myometrial LPAR1, LPAR3 and LPAR5 mRNA transcription was observed during the follicular phase in mares with category IIA endometrium in comparison to their expression in category I endometrium (P < 0.05). During endometrosis progression LPA reduced the force of myometrial contractions in both phases of the estrous cycle (P < 0.05). However, in mares with category IIA endometrium during the follicular phase, LPA was found to increase the force of contraction of myometrial strips in comparison to mares with category I endometrium (P < 0.01). Conclusions: In the course of endometrosis in mares, a disruption in the myometrial mRNA transcription of LPARs has been observed. This is the first study to examine the impact of LPA on myometrial contractility at diffrent stage of endometrosis. However, it is essential to consider that multiple factors may contribute to this process. Alternations in contractile activity and changes in myometrial LPARs mRNA transcription may indicate impaired LPA-signaling mechanisms in equine myometrium during endometrosis.
© 2024. The Author(s).
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Publication Date: 2024-12-19 PubMed ID: 39696406PubMed Central: PMC11658124DOI: 10.1186/s12917-024-04384-2Google Scholar: Lookup
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  • Journal Article

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article investigates how lysophosphatidic acid (LPA) affects the contraction of the myometrium muscle (which forms the uterine wall) and mRNA transcription of its receptors during different stages of endometrosis in mares. Endometrosis is a condition causing changes to the equine endometrium that may affect reproductive function.

Objective of the Study

  • The main goal of this study is to map the expression of myometrial LPAR1-6 mRNA, and the effects of LPA on myometrial contractions in mares suffering from endometrosis during the mid-luteal and follicular phases of the estrous cycle. The researchers sought to understand if and how LPA and its receptors (LPARs) influence uterine contractility in mares afflicted by endometrosis.

Findings of the Study

  • Different degrees of transcription changes were observed in myometrial LPAR1, LPAR3, LPAR5, and LPAR6 mRNA during different stages of endometrosis. In the mid-luteal phase, myometrial LPAR1 mRNA transcription was reduced in mares with endometrosis. An upregulation of myometrial LPAR3 or LPAR6 mRNA was observed in mares with category III or IIB endometria. An increase in myometrial LPAR1, LPAR3, and LPAR5 mRNA transcription was observed during the follicular phase in mares with category IIA endometrium.
  • The LPA was found to have varied effects on myometrial contractility depending on the stage of endometrosis. In general, LPA reduced the force of myometrial contractions in both phases of the estrous cycle. However, in mares with category IIA endometrium (lesions between glands) during the follicular phase, LPA was found to increase the force of contraction of myometrial strips.

Conclusion

  • The researchers concluded that endometrosis in mares leads to disrupted myometrial mRNA transcription of LPARs. This understanding is significant because it indicates that LPA-signaling mechanisms in equine myometrium might be impaired during endometrosis, which could have broader implications on the female reproductive function and embryo transport.
  • Additionally, the study suggests that multiple factors may contribute to myometrial contractility during endometrosis, and further research is required to fully elucidate this complex process.

Cite This Article

APA
Piotrowska-Tomala KK, Szóstek-Mioduchowska A, Jonczyk AW, Drzewiecka EM, Wrobel MH, Hojo T, Ferreira-Dias G, Skarzynski DJ. (2024). 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, 20(1), 571. https://doi.org/10.1186/s12917-024-04384-2

Publication

BMC veterinary research
ISSN: 1746-6148
NlmUniqueID: 101249759
Country: England
Language: English
Volume: 20
Issue: 1
Pages: 571
PII: 571

Researcher Affiliations

Piotrowska-Tomala, Katarzyna Karolina
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
Szóstek-Mioduchowska, Anna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
Jonczyk, Agnieszka Walentyna
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
Drzewiecka, Ewa Monika
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
Wrobel, Michał Hubert
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
Hojo, Takuo
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland.
  • Kyushu Okinawa Agricultural Research Center, NARO, 2421, Suya, Koshi, Kumamoto, 861-1192, Japan.
Ferreira-Dias, Graca
  • Faculty of Veterinary Medicine, C.I.I.S.A, University of Lisbon, Lisbon, Portugal.
  • AL4AnimalS-Associate Laboratory for Animal and Veterinary Sciences, Lisbon, Portugal.
Skarzynski, Dariusz Jan
  • Institute of Animal Reproduction and Food Research, Polish Academy of Sciences, 10-748, Olsztyn, Poland. d.skarzynski@pan.olsztyn.pl.

MeSH Terms

  • Animals
  • Horses
  • Female
  • Horse Diseases / physiopathology
  • Horse Diseases / genetics
  • Myometrium / drug effects
  • Myometrium / metabolism
  • Receptors, Lysophosphatidic Acid / genetics
  • Receptors, Lysophosphatidic Acid / metabolism
  • Lysophospholipids / pharmacology
  • RNA, Messenger / metabolism
  • RNA, Messenger / genetics
  • Uterine Contraction / drug effects
  • Endometriosis / veterinary
  • Endometriosis / genetics
  • Estrous Cycle / drug effects

Grant Funding

  • 2011/02/A/NZ5/00338 / Narodowe Centrum Nauki
  • BPN/BPT/2021/1/00026/U/00001 / Narodowa Agencja Wymiany Akademickiej

Conflict of Interest Statement

Declarations. Ethics approval and consent to participate: All material collection procedures were approved by the Local Ethics Committee for Experiments on Animals in Olsztyn, Poland (Agreements No. 51/2011). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

References

This article includes 77 references
  1. Kenney RM. Cyclic and pathologic changes of the mare endometrium as detected by biopsy, with a note on early embryonic death.. J Am Vet Med Assoc 1978;172:241–62.
    pubmed: 621166
  2. Kenney RM, Doig PA. Equine endometrial biopsy. 1986. p. 723–29.
  3. Hoffmann C, Ellenberger C, Mattos RC, Aupperle H, Dhein S, Stief B, Schoon HA. The equine endometrosis: new insights into the pathogenesis. Anim Reprod Sci 2009;111:261–78.
    pubmed: 18468817doi: 10.1016/j.anireprosci.2008.03.019google scholar: lookup
  4. Buczkowska J, Kozdrowski R, Nowak M, Raś A, Mrowiec J. Endometrosis-significance for horse reproduction, pathogenesis, diagnosis, and proposed therapeutic methods. Pol J Vet Sci 2014;17:547–54.
    pubmed: 25286671doi: 10.2478/pjvs-2014-0083google scholar: lookup
  5. Szóstek AZ, Siemieniuch MJ, Lukasik K, Galvão AM, Ferreira-Dias GM, Skarzynski DJ. mRNA transcription of prostaglandin synthases and their products in the equine endometrium in the course of fibrosis. Theriogenology 2012;78:768–76.
    pubmed: 22578628doi: 10.1016/j.theriogenology.2012.03.024google scholar: lookup
  6. Szóstek AZ, Lukasik K, Galvão AM, Ferreira-Dias GM, Skarzynski DJ. Impairment of the interleukin system in equine endometrium during the course of endometrosis. Biol Reprod 2013;89:79.
    pubmed: 23946535doi: 10.1095/biolreprod.113.10944735google scholar: lookup
  7. Gray CA, Bartol FF, Tarleton BJ, Wiley AA, Johnson GA, Bazer FW. Developmental biology of uterine glands. Biol Reprod 2016;5:1311–23.
    pubmed: 11673245doi: 10.1095/biolreprod65.5.1311google scholar: lookup
  8. 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 2019;124:9–17.
    pubmed: 30321755doi: 10.1016/j.theriogenology.2018.10.005google scholar: lookup
  9. 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;10:1119.
    pmc: PMC6981191pubmed: 31980722doi: 10.1038/s41598-020-58109-0google scholar: lookup
  10. 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;13:16263.
    pmc: PMC10533846pubmed: 37758834doi: 10.1038/s41598-023-43359-5google scholar: lookup
  11. Hanada M, Maeda Y, Oikawa MA. Histopathological Characteristics of Endometrosis in Thoroughbred Mares in Japan: Results from 50 Necropsy Cases. J Equine Sci 2014;25:45–52.
    pmc: PMC4090358pubmed: 25013358doi: 10.1294/jes.25.45google scholar: lookup
  12. LeBlanc MM, Johnson RD, Calderwood-Mays MB, Valderrama C. Lymphatic clearance of India ink in reproductively normal mares and mares susceptible to endometritis. Biol Reprod Monogr Ser 1995;1(52):501–6.
    doi: 10.1093/biolreprod/52.monograph_series1.501google scholar: lookup
  13. Troedsson MHT, Liu IKM. Uterine clearance of non-antigenic markers (51Cr) in response to a bacterial challenge in mares potentially susceptible and resistant to chronic uterine infections. J Reprod Fertil Suppl 1991;44:283–8.
    pubmed: 1795272
  14. Troedsson MHT, Liu IKM, Ing M, Pascoe J, Thurmond M. Multiple site electromyography recordings of uterine activity following an intrauterine bacterial challenge in mares susceptible and resistant to chronic uterine infection. J Reprod Fertil 1993;99:307–13.
    pubmed: 8107011doi: 10.1530/jrf.0.0990307google scholar: lookup
  15. Gaits F, Fourcade O, Le Balle F, Gueguen G, Gaige B, Gassama-Diagne A, Fauvel J, Salles JP, Mauco G, Simon MF, Chap H. Lysophosphatidic acid as a phospholipid mediator: pathways of synthesis. FEBS Lett 1997;410:54–8.
    pubmed: 9247122doi: 10.1016/s0014-5793(97)00411-0google scholar: lookup
  16. Noguchi K, Ishii S, Shimizu T. Identification of p2y 9/GPR23 as a novel G protein-coupled receptor for Lysophosphatidic acid, structurally distant from the Edg family. J Biol Chem 2003;278:25600–6.
    pubmed: 12724320doi: 10.1074/jbc.m302648200google scholar: lookup
  17. Anliker B, Chun J. Cell surface receptors in lysophospholipid signaling. Semin Cell Dev Biol 2004;15:457–65.
    pubmed: 15271291doi: 10.1016/j.semcdb.2004.05.005google scholar: lookup
  18. Aoki J. Mechanisms of lysophosphatidic acid production. Semin Cell Dev Biol 2004;15:477–89.
    pubmed: 15271293doi: 10.1016/j.semcdb.2004.05.001google scholar: lookup
  19. Lin M, Herr DR, Chun J. Lysophosphatidic acid (LPA) receptors: signaling properties and disease relevance. Prostaglandins Other Lipid Mediat 2010;91:130–8.
    pmc: PMC2845529pubmed: 20331961doi: 10.1016/j.prostaglandins.2009.02.002google scholar: lookup
  20. Yung YC, Stoddard NC, Chun J. LPA receptor signaling: pharmacology, physiology, and pathophysiology. J Lipid Res 2014;55:1192–214.
    pmc: PMC4076099pubmed: 24643338doi: 10.1194/jlr.r046458google scholar: lookup
  21. van Meeteren LA, Moolenaar WH. Regulation and biological activities of the autotaxin-LPA axis. Prog Lipid Res 2007;46:145–60.
    pubmed: 17459484doi: 10.1016/j.plipres.2007.02.001google scholar: lookup
  22. Tokumura A, Fukuzawa K, Yamada S, Tsukatani H. Stimulatory effect of lysophosphatidic acids on uterine smooth muscles of non-pregnant rats. Arch Int Pharmacodyn Ther 1980;245:74–83.
    pubmed: 6902643
  23. Kurusu S, Terashima R, Sugiyama M, Tanaka M, Kadowaki T, Kizaki K, Kawaminami M. Expression of lysophosphatidic acid receptors in the rat uterus: cellular distribution of protein and gestation-associated changes in gene expression. J Vet Med Sci 2023;85(11):1165–71.
    pmc: PMC10686777pubmed: 37779089doi: 10.1292/jvms.23-0336google scholar: lookup
  24. Ye X, Hama K, Contos JJ, Anliker B, Inoue A, Skinner MK, Suzuki H, Amano T, Kennedy G, Arai H, Aoki J, Chun J. LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 2005;435:104–8.
    pmc: PMC1369590pubmed: 15875025doi: 10.1038/nature03505google scholar: lookup
  25. Seo H, Kim M, Choi Y, Lee CK, Ka H. Analysis of lysophosphatidic acid (LPA) receptor and LPA-induced endometrial prostaglandin-endoperoxide synthase 2 expression in the porcine uterus. Endocrinology 2008;149:6166–75.
    pubmed: 18703629doi: 10.1210/en.2008-0354google scholar: lookup
  26. Woclawek-Potocka I, Komiyama J, Saulnier-Blache JS, Brzezicka E, Bah MM, Okuda K, Skarzynski DJ. Lysophosphatic acid modulates prostaglandin secretion in the bovine uterus. Reproduction 2009;137:95–105.
    pubmed: 18829944doi: 10.1530/rep-08-0209google scholar: lookup
  27. Woclawek-Potocka I, Kowalczyk-Zieba I, Skarzynski DJ. Lysophosphatidic acid action during early pregnancy in the cow: in vivo and in vitro studies. J Reprod Dev 2010;56:411–20.
    pubmed: 20431249doi: 10.1262/jrd.09-205google scholar: lookup
  28. Boruszewska D, Kowalczyk-Zieba I, Piotrowska-Tomala K, Saulnier-Blache JS, Acosta T, Skarzynski DJ, Woclawek-Potocka I. Which bovine endometrial cells are the source of and target for lysophosphatidic acid?. Reprod Biol 2013;13(1):100–3.
    pubmed: 23522079doi: 10.1016/j.repbio.2013.01.166google scholar: lookup
  29. Boruszewska D, Sinderewicz E, Kowalczyk-Zieba I, Skarzynski DJ, Woclawek-Potocka I. Influence of lysophosphatidic acid on estradiol production and follicle stimulating hormone action in bovine granulosa cells. Reprod Biol 2013;13:344–7.
    pubmed: 24287044
  30. Liszewska E, Reinaud P, Billon-Denis E, Dubois O, Robin P, Charpigny G. Lysophosphatidic acid signaling during embryo development in sheep: involvement in prostaglandin synthesis. Endocrinology 2009;150:422–34.
    pubmed: 18772233doi: 10.1210/en.2008-0749google scholar: lookup
  31. Liszewska E, Reinaud P, Dubois O, Charpigny G. Lysophosphatidic acid receptors in ovine uterus during estrous cycle and early pregnancy and their regulation by progesterone. Domest Anim Endocrinol 2012;42:31–42.
    pubmed: 22032854doi: 10.1016/j.domaniend.2011.08.003google scholar: lookup
  32. Gogarten W, Emala CW, Lindeman KS, Hirshman CA. Oxytocin and Lysophosphatidic Acid Induce Stress Fiber Formation in Human Myometrial Cells via a Pathway Involving Rho-Kinase. Biol Reprod 2001;65:401–6.
    pubmed: 11466206doi: 10.1095/biolreprod65.2.401google scholar: lookup
  33. Nagashima S, Kimura T, Terashima R, Sugiyama M, Kizaki K, Kawaminami M, Kurusu S. Lysophosphatidic acid stimulates rat uterine contraction in vitro. J Reprod Dev 2023;69:163–9.
    pmc: PMC10267583pubmed: 37045747doi: 10.1262/jrd.2023-011google scholar: lookup
  34. Markiewicz W, Kamińska K, Bogacki M, Maślanka T, Jaroszewski J. Participation of analogues of lysophosphatidic acid (LPA): oleoyl-sn-glycero-3-phosphate (L-α-LPA) and 1-oleoyl-2-O-methyl-rac-glycerophosphothionate (OMPT) in uterine smooth muscle contractility of the pregnant pigs. Pol J Vet Sci 2012;15:635–43.
    pubmed: 23390752doi: 10.2478/v10181-012-0100-9google scholar: lookup
  35. Causey RC. Mucus and the mare: How little we know. Theriogenology 2007;68:386–94.
    pubmed: 17512579doi: 10.1016/j.theriogenology.2007.04.011google scholar: lookup
  36. Christoffersen M, Troedsson M. Inflammation and fertility in the mare. Reprod Domest Anim 2017;52:4–20.
    pubmed: 28815848doi: 10.1111/rda.13013google scholar: lookup
  37. Watson ED, Sertich PL. Prostaglandin production by horse embryos and the effect of co-culture of embryos with endometrium from pregnant mares. J Reprod Fertil 1989;87:331–6.
    pubmed: 2621704doi: 10.1530/jrf.0.0870331google scholar: lookup
  38. Hirsbrunner G, Reist M, Couto SS, Steiner A, Snyder J, Vanleeuwen E, Liu I. An in vitro study on spontaneous myometrial contractility in the mare during estrus and diestrus. Theriogenology 2006;65:517–27.
    pubmed: 15993483doi: 10.1016/j.theriogenology.2005.05.048google scholar: lookup
  39. Aguilar HN, Mitchell BF. Physiological pathways and molecular mechanisms regulating uterine contractility. Hum Reprod Update 2010;16:725–44.
    pubmed: 20551073doi: 10.1093/humupd/dmq016google scholar: lookup
  40. Szóstek-Mioduchowska A, Leciejewska N, Zelmańska B, Staszkiewicz-Chodor J, Ferreira-Dias G, Skarzynski D. 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 2020;16:343.
    pmc: PMC7499873pubmed: 32943074doi: 10.1186/s12917-020-02562-6google scholar: lookup
  41. Roberto da Costa RP, Serrão PM, Monteiro S, Pessa P, Silva JR, Ferreira-Dias G. Caspase-3-mediated apoptosis and cell proliferation in the equine endometrium during the oestrous cycle. Reprod Fertil Dev 2007;19: 925–932.
    pubmed: 18076824doi: 10.1071/rd06159google scholar: lookup
  42. Wrobel MH, Grzeszczyk M, Młynarczuk J, Kotwica J. The adverse effects of aldrin and dieldrin on both myometrial contractions and the secretory functions of bovine ovaries and uterus in vitro. Toxicol Appl Pharmacol 2015;285:23–31.
    pubmed: 25771128doi: 10.1016/j.taap.2015.03.005google scholar: lookup
  43. Andersen C, Jensen JL, Ørntoft TF. Normalization of real-time quantitative reverse transcription-PCR data: A model-based variance estimation approach to identify genes suited for normalization, applied to bladder and colon cancer data sets. Cancer Res 2004;64:5245–50.
    pubmed: 15289330doi: 10.1158/0008-5472.can-04-0496google scholar: lookup
  44. Wrobel M, Kaminski K, Kotwica J. In vitro effects of polychlorinated biphenyls (PCBs) on the contractility of bovine myometrium from the periovulatory stage of the estrous cycle. Reprod Biol 2005;5:303–19.
    pubmed: 16372047
  45. Wrobel MH, Rekawiecki R, Kotwica J. Involvement of prostaglandin F2α in the adverse effect of PCB 77 on the force of contractions of bovine myometrium. Toxicology 2009;262:224–9.
    pubmed: 19549555doi: 10.1016/j.tox.2009.06.012google scholar: lookup
  46. Szóstek AZ, Siemieniuch MJ, Galvão AM, Lukasik K, Zieba D, Ferreira-Dias GM, Skarzynski DJ. Effects of cell storage and passage on basal and oxytocin-regulated prostaglandin secretion by equine endometrial epithelial and stromal cells. Theriogenology 2012;77:1698–708.
    pubmed: 22357062doi: 10.1016/j.theriogenology.2011.12.015google scholar: lookup
  47. Kotwica G, Kurowicka B, Franczaka A, Grzegorzewski W, Wrobel M, Mlynarczuk J, Kotwica J. The concentrations of catecholamines and oxytocin receptors in the oviduct and its contractile activity in cows during the estrous cycle. Theriogenology 2003;60:953–64.
    pubmed: 12935872
  48. Korzekwa AJ, Lukasik K, Pilawski W, Piotrowska-Tomala KK, Jaroszewski JJ, Yoshioka S, Okuda K, Skarzynski DJ. Influence of prostaglandin F₂α analogues on the secretory function of bovine luteal cells and ovarian arterial contractility in vitro. Vet J 2014;199:131–7.
    pubmed: 24268486doi: 10.1016/j.tvjl.2013.09.021google scholar: lookup
  49. Geraldo LHM, Spohr TCLdS, Amaral RFd, Fonseca ACCd, Garcia C, Mendes FdA, dosSantos MF, Lima FRS. Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies. Sig Transduct Target Ther 2021;6:45.
    pmc: PMC7851145pubmed: 33526777
  50. Kaminska K, Wasielak M, Bogacka I, Blitek M, Bogacki M. Quantitative expression of lysophosphatidic acid receptor 3 gene in porcine endometrium during the periimplantation period and estrous cycle. Prostaglandins Other Lipid Mediat 2008;85:26–32.
    pubmed: 18024221doi: 10.1016/j.prostaglandins.2007.10.001google scholar: lookup
  51. Kowalczyk-Zieba I, Boruszewska D, Saulnier-Blache JS, Da Costa LL, Jankowska K, Skarzynski DJ, Woclawek-Potocka I. Lysophosphatidic acid action in the bovine corpus luteum—an in vitro study. J Reprod Dev 2012;58:661–71.
    pubmed: 22972186doi: 10.1262/jrd.2012-060google scholar: lookup
  52. Sadam A, Parida S, Padol AR, Verma AD, Baba NA, Khuman WM, Srivastava V, Panigrahi M, Singh TU, Sarkar SN. Study of lysophosphatidic acid receptors (LPARs) in buffalo uterus demonstrated upregulation of LPAR1 and LPAR6 in early pregnancy. Theriogenology 2017;87:90–7.
    pubmed: 28708504doi: 10.1016/j.theriogenology.2017.05.019google scholar: lookup
  53. Yukiura H, Kano K, Kise R, Inoue A, Aoki J. LPP3 localizes LPA6 signalling to non-contact sites in endothelial cells. J Cell Sci 2015;128:3871–7.
    pmc: PMC4657331pubmed: 26345369doi: 10.1242/jcs.172098google scholar: lookup
  54. Hama K, Aoki J, Bandoh K, Inoue A, Endo T, Amano T, Suzuki H, Arai H. Lysophosphatidic receptor, LPA3, is positively and negatively regulated by progesterone and estrogen in the mouse uterus. Life Sci 2006;79:1736–40.
    pubmed: 16815476
  55. Ye X, Herr DR, Diao H, Rivera R, Chun J. Unique uterine localization and regulation may differentiate LPA3 from other lysophospholipid receptors for its role in embryo implantation. Fertil Steril 2011;95:2107–13.
    pmc: PMC3084612pubmed: 21411082
  56. LeBlanc MM, Causey RC. Clinical and subclinical endometritis in the mare: both threats to fertility. Reprod Domest Anim 2009;44(Suppl 3):10–22.
    pubmed: 19660076doi: 10.1111/j.1439-0531.2009.01485.xgoogle scholar: lookup
  57. Canisso IF, Segabinazzi LGTM, Fedorka CE. Persistent Breeding-Induced Endometritis in Mares - a Multifaceted Challenge: From Clinical Aspects to Immunopathogenesis and Pathobiology. Int J Mol Sci 2020;21:1432.
    pmc: PMC7073041pubmed: 32093296doi: 10.3390/ijms21041432google scholar: lookup
  58. Katila T, Ferreira-Dias G. Evolution of the Concepts of Endometrosis, Post Breeding Endometritis, and Susceptibility of Mares. Animals (Basel) 2022;12:779.
    pmc: PMC8944725pubmed: 35327176doi: 10.3390/ani12060779google scholar: lookup
  59. Skarzynski DJ, Szóstek-Mioduchowska AZ, Rebordão MR, Jalali BM, Piotrowska-Tomala KK, Leciejewska N, Łazarczyk M, Ferreira-Dias GM. Neutrophils, monocytes and other immune components in the equine endometrium: Friends or foes?. Theriogenology 2020;150:150–7.
    pubmed: 31973963doi: 10.1016/j.theriogenology.2020.01.018google scholar: lookup
  60. 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;11:2615.
    pmc: PMC8469524pubmed: 34573581doi: 10.3390/ani11092615google scholar: lookup
  61. Patil RK, Sinha SN, Einarsson S, Settergren I. The effect of prostaglandin F2 alpha and oxytocin on bovine myometrium in vitro. Nord Vet Med 1980;32:474–9.
    pubmed: 7195017
  62. Ousey JC, Freestone N, Fowden AL, Mason WT, Rossdale PD. The effects of oxytocin and progestagens on myometrial contractility in vitro during equine pregnancy. J Reprod Fertil Suppl 2000;56:681–91.
    pubmed: 20681184
  63. Rigby SL, Barhoumi R, Burghardt RC, Colleran P, Thompson JA, Varner DD, Blanchard TL, Brinsko SP, Taylor T, Wilkerson MK, Delp MD. Mares with delayed uterine clearance have an intrinsic defect in myometrial function. Biol Reprod 2001;65:740–7.
    pubmed: 11514336doi: 10.1095/biolreprod65.3.740google scholar: lookup
  64. Hama K, Aoki J, Inoue A, Endo T, Amano T, Motoki R, Kanai M, Ye X, Chun J, Matsuki N, Suzuki H, Shibasaki M, Arai H. Embryo spacing and implantation timing are differentially regulated by LPA3-mediated lysophosphatidic acid signaling in mice. Biol Reprod 2007;77:954–9.
    pubmed: 17823089doi: 10.1095/biolreprod.107.060293google scholar: lookup
  65. Toews ML, Ustinova EE, Schultz HD. Lysophosphatidic acid enhances contractility of isolated airway smooth muscle. J Appl Physiol 1997;83:1216–22.
    pubmed: 9338431doi: 10.1152/jappl.1997.83.4.1216google scholar: lookup
  66. Stoddard NC, Chun J. Promising pharmacological directions in the world of lysophosphatidic Acid signaling. Biomol. Ther. (Seoul.) 2015; 23:1–11.
    pmc: PMC4286743pubmed: 25593637doi: 10.4062/biomolther.2014.109google scholar: lookup
  67. Choi JW, Herr DR, Noguchi K, Yung YC, Lee CW, Mutoh T, Lin ME, Teo ST, Park KE, Mosley AN, Chun J. LPA Receptors: Subtypes and Biological Actions. Annu Rev Pharmacol Toxicol 2010;50:157–86.
    pubmed: 20055701doi: 10.1146/annurev.pharmtox.010909.105753google scholar: lookup
  68. Cummings R, Zhao Y, Jacoby D, Spannhake EW, Ohba M, Garcia JG, Watkins T, He D, Saatian B, Natarajan V. Protein kinase Cdelta mediates lysophosphatidic acid-induced NF-kappaB activation and interleukin-8 secretion in human bronchial epithelial cells. J Biol Chem 2004;279:41085–94.
    pubmed: 15280372
  69. Schumacher KA, Classen HG, Spath M. Platelet aggregation evoked in vitro and in vivo by phosphatidic acids and lysoderivatives: identity with substances in aged serum (DAS). Thromb Haemost 1979;42:631–40.
    pubmed: 116384
  70. Zhao Y, Natarajan V. Lysophosphatidic acid signaling in airway epithelium: Role in airway inflammation and remodeling. Cell Signal 2013;25:2076–83.
    pmc: PMC2660380pubmed: 18996473
  71. Tigyi G. Aiming drug discovery at lysophosphatidic acid targets. Br. J Pharmacol 2010;159:241–70.
    pmc: PMC2989581pubmed: 20735414
  72. Piotrowska-Tomala KK, Jonczyk AW, Skarzynski DJ, Szóstek-Mioduchowska AZ. Luteinizing hormone and ovarian steroids affect in vitro prostaglandin production in the equine myometrium and endometrium. Theriogenology 2020;153:1–8.
    pubmed: 32416544doi: 10.1016/j.theriogenology.2020.04.039google scholar: lookup
  73. Dancs PT, Ruisanchez É, Balogh A, Panta CR, Miklós Z, Nüsing RM, Aoki J, Chun J, Offermanns S, Tigyi G, Benyó Z. LPA1 receptor-mediated thromboxane A2 release is responsible for lysophosphatidic acid-induced vascular smooth muscle contraction. FASEB J 2017;31:1547–55.
    pmc: PMC5349804pubmed: 28069828doi: 10.1096/fj.201600735rgoogle scholar: lookup
  74. Esteller-Vico A, Liu IKM, Vaughan B, Steffey EP, Brosnan RJ. Effects of vascular elastosis on uterine blood flow and perfusion in anesthetized mares. Theriogenology 2015;83:988–94.
    pubmed: 25543154
  75. Esteller-Vico A, Liu IKM, Vaughan B, Steffey EP, Brosnan RJ. Effects of estradiol on uterine perfusion in anesthetized cyclic mares affected with uterine vascular elastosis. Anim Reprod Sci 2016;164:57–63.
    pubmed: 26642749
  76. Ricketts SW, Alonso S. The effect of age and parity on the development of equine chronic endometrial disease. Equine Vet J 1991;23:189–92.
    pubmed: 1884699doi: 10.1111/j.2042-3306.1991.tb02752.xgoogle scholar: lookup
  77. Ebert A, Schoon D, Schoon HA. Age-related endometrial alterations in mares—biopsy findings of the last 20 years. 2014; 2: 230–232.

Citations

This article has been cited 1 times.
  1. Wang S, Zhang Y, Zhang X, Cai X, Hong M. Lysophosphatidic acid promotes endometrial decidualization in recurrent implantation failure patients by regulating LPAR6. Front Cell Dev Biol 2025;13:1652740.
    doi: 10.3389/fcell.2025.1652740pubmed: 41199770google scholar: lookup
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