FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
International journal of molecular sciences2026; 27(3); 1550; doi: 10.3390/ijms27031550

Activation of the S100A8/A9 Alarmin Amplifies Inflammatory Pathways in Equine Ascending Placentitis.

Abstract: Ascending placentitis is a significant cause of equine pregnancy loss, yet the upstream inflammatory triggers are poorly defined. Recently, we identified S100A8/S100A9 (S100A8/A9) alarmins as potential upstream regulators in a chronic equine placentitis model. The current study aimed to determine whether this upregulation is sustained in the acute model and in clinical cases, and to elucidate the expression of their downstream inflammatory mediators. Using an experimental model, we quantified mRNA expression in acute ( = 5) and chronic ( = 6) placentitis induced by ssp. . We found mRNA expression of and was significantly upregulated in chorioallantois during both acute ( < 0.001) and chronic ( < 0.0001) disease compared to controls ( = 5), demonstrating their role is not limited to chronic pathology. A strong positive correlation ( = 0.945) underscored their coordinated expression. Immunohistochemistry revealed minimal staining in controls but dense infiltrations of S100A8/A9-positive neutrophils and macrophages in placentitis tissues. To define the clinical relevance of the downstream pathway, we analyzed RNA sequencing data from clinical placentitis cases (placentitis, = 4) compared to normal postpartum placenta (control, = 4). This confirmed upregulation of and revealed a concurrent increase in their receptors (, ) and a spectrum of NF-κB-driven effectors, including pro-inflammatory cytokines (, , ), chemokines (, , ), and the apoptotic mediator . Our findings establish that S100A8/A9 upregulation is a sustained feature of equine placentitis and delineates a coherent S100A8/A9-TLR4/RAGE-NF-κB signaling axis that drives inflammation and tissue damage in clinical disease. These findings highlight the diagnostic potential of S100A8/A9 and position this alarmin system as a promising therapeutic target for mitigating infection-induced pregnancy loss.
Get Full Text
Publication Date: 2026-02-04 PubMed ID: 41683969PubMed Central: PMC12897833DOI: 10.3390/ijms27031550Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.

Overview

  • The study explores the role of the S100A8/A9 protein complex (alarmins) in triggering and amplifying inflammation in equine ascending placentitis, a major cause of pregnancy loss in horses.
  • The research demonstrates that S100A8/A9 is upregulated in both acute and chronic forms of placentitis and identifies downstream inflammatory pathways activated by these alarmins, suggesting potential diagnostic and therapeutic implications.

Background and Purpose

  • Equine ascending placentitis: A serious infectious disease causing inflammation of the placenta, leading to pregnancy loss in horses.
  • Knowledge gap: The early molecular triggers and inflammatory mechanisms driving the disease are not well understood.
  • S100A8/A9 alarmins: Known damage-associated molecular pattern (DAMP) proteins that can activate immune responses and inflammation; previously implicated in chronic equine placentitis.
  • Objective: To determine if S100A8/A9 upregulation also occurs in acute placentitis, and to investigate the downstream inflammatory signaling pathways activated by these proteins in both experimental and clinical cases.

Methods

  • Experimental model: Induced placentitis in horses using bacterial infection (Streptococcus equi ssp.), with groups for acute placentitis (n=5), chronic placentitis (n=6), and healthy controls (n=5).
  • Gene expression analysis: Measured mRNA levels of S100A8 and S100A9 in placental tissues using quantitative techniques to assess their expression during acute and chronic disease.
  • Immunohistochemistry: Localized S100A8/A9 proteins in tissue sections to identify cell types involved and intensity of inflammatory infiltration.
  • RNA sequencing data: Analyzed samples from naturally occurring (clinical) placentitis cases (n=4) versus normal postpartum placentas (n=4) to identify broader changes in inflammatory mediator expression downstream of S100A8/A9.

Key Findings

  • S100A8/A9 mRNA upregulation: Significantly increased expression in the chorioallantois tissue during both acute (p<0.001) and chronic (p<0.0001) placentitis compared to controls.
  • Coordinated expression: High positive correlation (r=0.945) between S100A8 and S100A9, indicating that these alarmins are co-regulated during placental inflammation.
  • Cellular localization: Immunohistochemistry showed minimal staining in healthy placentas, but dense infiltration of neutrophils and macrophages positive for S100A8/A9 in diseased tissue, highlighting their immune cell source.
  • Downstream inflammatory pathways: RNA-seq data from clinical cases revealed not only upregulation of S100A8/A9 but also increased expression of their receptors TLR4 and RAGE.
  • Activated signaling axis: Evidence of activation of the NF-κB pathway, a key transcription factor controlling inflammation.
  • Elevated inflammatory mediators: Increased levels of pro-inflammatory cytokines (e.g., IL-1β, IL-6, TNF-α), chemokines (e.g., CCL2, CXCL8, CXCL10), and apoptotic mediator expression, supporting the role of S100A8/A9 in driving inflammation and tissue damage.

Conclusions and Implications

  • S100A8/A9 are not only involved in chronic equine placentitis but also play a sustained and active role in acute inflammatory responses, amplifying disease severity.
  • The study outlines a clear mechanistic pathway: S100A8/A9 alarmins bind to innate immune receptors (TLR4 and RAGE), triggering NF-κB activation and release of various inflammatory mediators that contribute to placental inflammation and damage.
  • This signaling axis may serve as a biomarker for diagnosing placentitis due to its consistent upregulation in clinical cases.
  • Targeting the S100A8/A9-TLR4/RAGE-NF-κB pathway offers a promising therapeutic strategy to reduce inflammation-induced pregnancy loss in horses.
  • Further research could explore inhibitors or modulators of these alarmins or their downstream pathways for clinical interventions.

Cite This Article

APA
Scoggin KE, Rakha SI, Abdellatif AM, Adlan F, Helmy YA, Ruby R, Ball B, Boakari Y, Ali HE. (2026). Activation of the S100A8/A9 Alarmin Amplifies Inflammatory Pathways in Equine Ascending Placentitis. Int J Mol Sci, 27(3), 1550. https://doi.org/10.3390/ijms27031550

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 27
Issue: 3
PII: 1550

Researcher Affiliations

Scoggin, Kirsten E
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Rakha, Shimaa I
  • Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Abdellatif, Ahmed M
  • Department of Anatomy and Embryology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Adlan, Fatma
  • Department of Theriogenology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Helmy, Yosra A
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Ruby, Rebecca
  • Veterinary Diagnostic Laboratory, University of Kentucky, Lexington, KY 40511, USA.
Ball, Barry
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.
Boakari, Yatta
  • Department of Large Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A & M University, College Station, TX 77843, USA.
Ali, Hossam El-Sheikh
  • Maxwell H. Gluck Equine Research Center, Department of Veterinary Science, University of Kentucky, Lexington, KY 40546, USA.

MeSH Terms

  • Animals
  • Pregnancy
  • Calgranulin A / metabolism
  • Calgranulin A / genetics
  • Female
  • Calgranulin B / metabolism
  • Calgranulin B / genetics
  • Horses
  • Alarmins / metabolism
  • Alarmins / genetics
  • Horse Diseases / metabolism
  • Horse Diseases / microbiology
  • Horse Diseases / genetics
  • Horse Diseases / pathology
  • Inflammation / metabolism
  • Placenta Diseases / metabolism
  • Placenta Diseases / veterinary
  • Placenta Diseases / microbiology
  • Placenta Diseases / genetics
  • Placenta Diseases / pathology
  • Streptococcus equi
  • Streptococcal Infections / veterinary
  • Streptococcal Infections / metabolism
  • Streptococcal Infections / microbiology
  • Placenta / metabolism
  • Placenta / pathology
  • Placenta / microbiology
  • Signal Transduction

Grant Funding

  • N/A / Gluck Equine Research Foundation
  • N/A / 2024 Equine Research Award - Boehringer Ingelheim
  • HATCH #7009671 / USDA Capacity Project

Conflict of Interest Statement

The authors declare no conflicts of interest.

References

This article includes 65 references
  1. Loux SC, Fernandes CB, Dini P, Wang K, Wu X, Baxter D, Scoggin KE, Troedsson MHT, Squires EL, Ball BA. Small RNA (sRNA) expression in the chorioallantois, endometrium and serum of mares following experimental induction of placentitis.. Reprod. Fertil. Dev. 2019;31:1144–1156.
    doi: 10.1071/RD18400pubmed: 30947806google scholar: lookup
  2. LeBlanc MM. Ascending placentitis in the mare: An update.. Reprod. Domest. Anim. 2010;45:28–34.
    doi: 10.1111/j.1439-0531.2010.01633.xpubmed: 20591062google scholar: lookup
  3. Ousey JC, Houghton E, Grainger L, Rossdale PD, Fowden AL. Progestagen profiles during the last trimester of gestation in Thoroughbred mares with normal or compromised pregnancies.. Theriogenology 2005;63:1844–1856.
    doi: 10.1016/j.theriogenology.2004.08.010pubmed: 15823343google scholar: lookup
  4. Wynn MAA, Ball BA, May J, Esteller-Vico A, Canisso I, Squires E, Troedsson M. Changes in maternal pregnane concentrations in mares with experimentally-induced, ascending placentitis.. Theriogenology 2018;122:130–136.
    doi: 10.1016/j.theriogenology.2018.09.001pubmed: 30265893google scholar: lookup
  5. Morris S, Kelleman AA, Stawicki RJ, Hansen PJ, Sheerin PC, Sheerin BR, Paccamonti DL, LeBlanc MM. Transrectal ultrasonography and plasma progestin profiles identifies feto-placental compromise in mares with experimentally induced placentitis.. Theriogenology 2007;67:681–691.
    doi: 10.1016/j.theriogenology.2006.05.021pubmed: 17126392google scholar: lookup
  6. Wang S, Song R, Wang Z, Jing Z, Wang S, Ma J. S100A8/A9 in Inflammation.. Front. Immunol. 2018;9:1298.
    doi: 10.3389/fimmu.2018.01298pmc: PMC6004386pubmed: 29942307google scholar: lookup
  7. Pruenster M, Vogl T, Roth J, Sperandio M. S100A8/A9: From basic science to clinical application.. Pharmacol. Ther. 2016;167:120–131.
    doi: 10.1016/j.pharmthera.2016.07.015pubmed: 27492899google scholar: lookup
  8. Sreejit G, Flynn MC, Patil M, Krishnamurthy P, Murphy AJ, Nagareddy PR. S100 family proteins in inflammation and beyond.. Adv. Clin. Chem. 2020;98:173–231.
    pubmed: 32564786
  9. Ma L, Sun P, Zhang JC, Zhang Q, Yao SL. Proinflammatory effects of S100A8/A9 via TLR4 and RAGE signaling pathways in BV-2 microglial cells.. Int. J. Mol. Med. 2017;40:31–38.
    doi: 10.3892/ijmm.2017.2987pmc: PMC5466387pubmed: 28498464google scholar: lookup
  10. Zhou H, Zhao C, Shao R, Xu Y, Zhao W. The functions and regulatory pathways of S100A8/A9 and its receptors in cancers.. Front. Pharmacol. 2023;14:1187741.
    doi: 10.3389/fphar.2023.1187741pmc: PMC10493297pubmed: 37701037google scholar: lookup
  11. Xia P, Ji X, Yan L, Lian S, Chen Z, Luo Y. Roles of S100A8, S100A9 and S100A12 in infection, inflammation and immunity.. Immunology 2024;171:365–376.
    doi: 10.1111/imm.13722pubmed: 38013255google scholar: lookup
  12. Ieguchi K, Omori T, Komatsu A, Tomita T, Deguchi A, Maru Y. Ephrin-A1 expression induced by S100A8 is mediated by the toll-like receptor 4.. Biochem. Biophys. Res. Commun. 2013;440:623–629.
    doi: 10.1016/j.bbrc.2013.09.119pubmed: 24103748google scholar: lookup
  13. Vogl T, Tenbrock K, Ludwig S, Leukert N, Ehrhardt C, van Zoelen MA, Nacken W, Foell D, van der Poll T, Sorg C. Mrp8 and Mrp14 are endogenous activators of Toll-like receptor 4, promoting lethal, endotoxin-induced shock.. Nat. Med. 2007;13:1042–1049.
    doi: 10.1038/nm1638pubmed: 17767165google scholar: lookup
  14. Schelbergen RF, Blom AB, van den Bosch MH, Slöetjes A, Abdollahi-Roodsaz S, Schreurs BW, Mort JS, Vogl T, Roth J, van den Berg WB. Alarmins S100A8 and S100A9 elicit a catabolic effect in human osteoarthritic chondrocytes that is dependent on Toll-like receptor 4.. Arthritis Rheum. 2012;64:1477–1487.
    doi: 10.1002/art.33495pubmed: 22127564google scholar: lookup
  15. Jurewicz E, Filipek A. Ca(2+)- binding proteins of the S100 family in preeclampsia.. Placenta 2022;127:43–51.
    doi: 10.1016/j.placenta.2022.07.018pubmed: 35964380google scholar: lookup
  16. Mitranovici M.-I., Caravia L., Oală I.E., Tiron A.T., Buicu C.-F., Dumitrascu-Biris D., Munteanu M., Ivan V., Apostol A., Petre I.. Exploring the Relevance of S100A8 and S100A9 Proteins in Preeclampsia: A Narrative Review. Int. J. Mol. Sci. 2025;26:10118.
    doi: 10.3390/ijms262010118pmc: PMC12564266pubmed: 41155408google scholar: lookup
  17. Nair R.R., Khanna A., Singh K.. Role of inflammatory proteins S100A8 and S100A9 in pathophysiology of recurrent early pregnancy loss. Placenta 2013;34:824–827.
    doi: 10.1016/j.placenta.2013.06.307pubmed: 23850136google scholar: lookup
  18. Nair R.R., Khanna A., Singh K.. Association of increased S100A8 serum protein with early pregnancy loss. Am. J. Reprod. Immunol. 2015;73:91–94.
    doi: 10.1111/aji.12318pubmed: 25252120google scholar: lookup
  19. Gravett M.G., Novy M.J., Rosenfeld R.G., Reddy A.P., Jacob T., Turner M., McCormack A., Lapidus J.A., Hitti J., Eschenbach D.A.. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA 2004;292:462–469.
    doi: 10.1001/jama.292.4.462pubmed: 15280344google scholar: lookup
  20. Cozac D.A., Halațiu V.B., Scridon A.. The alarmin tandem: Unraveling the complex effect of S100A8/A9—From atherosclerosis to cardiac arrhythmias. Front. Immunol. 2025;16:1630410.
    doi: 10.3389/fimmu.2025.1630410pmc: PMC12422909pubmed: 40948795google scholar: lookup
  21. García-Domínguez M.. Relationship of S100 Proteins with Neuroinflammation. Biomolecules 2025;15:1125.
    doi: 10.3390/biom15081125pmc: PMC12384525pubmed: 40867570google scholar: lookup
  22. Tian Q., Li Z., Yan Z., Jiang S., Zhao X., Wang L., Li M.. Inflammatory role of S100A8/A9 in the central nervous system non-neoplastic diseases. Brain Res. Bull. 2024;218:111100.
    doi: 10.1016/j.brainresbull.2024.111100pubmed: 39396712google scholar: lookup
  23. El-Sheikh Ali H., Boakari Y.L., Loux S.C., Dini P., Scoggin K.E., Esteller-Vico A., Kalbfleisch T., Ball B.A.. Transcriptomic analysis reveals the key regulators and molecular mechanisms underlying myometrial activation during equine placentitis†. Biol. Reprod. 2020;102:1306–1325.
    doi: 10.1093/biolre/ioaa020pubmed: 32065222google scholar: lookup
  24. Ricard R.M., St-Jean G., Duizer G., Atwal H., Wobeser B.K.. A 13-year retrospective study of equine abortions in Canada. Can. Vet. J. 2022;63:715–721.
    pmc: PMC9207963pubmed: 35784776
  25. Agerholm J.S., Klas E.M., Damborg P., Borel N., Pedersen H.G., Christoffersen M.. A Diagnostic Survey of Aborted Equine Fetuses and Stillborn Premature Foals in Denmark. Front. Vet. Sci. 2021;8:740621.
    doi: 10.3389/fvets.2021.740621pmc: PMC8631530pubmed: 34859085google scholar: lookup
  26. Macleay C.M., Carrick J., Shearer P., Begg A., Stewart M., Heller J., Chicken C., Brookes V.J.. A Scoping Review of the Global Distribution of Causes and Syndromes Associated with Mid- to Late-Term Pregnancy Loss in Horses between 1960 and 2020. Vet. Sci. 2022;9:186.
    doi: 10.3390/vetsci9040186pmc: PMC9032147pubmed: 35448683google scholar: lookup
  27. Giles R.C., Donahue J.M., Hong C.B., Tuttle P.A., Petrites-Murphy M.B., Poonacha K.B., Roberts A.W., Tramontin R.R., Smith B., Swerczek T.W.. Causes of abortion, stillbirth, and perinatal death in horses: 3527 cases (1986–1991). J. Am. Vet. Med. Assoc. 1993;203:1170–1175.
    doi: 10.2460/javma.1993.203.08.1170pubmed: 8244867google scholar: lookup
  28. Spratt D.E., Barber K.R., Marlatt N.M., Ngo V., Macklin J.A., Xiao Y., Konermann L., Duennwald M.L., Shaw G.S.. A subset of calcium-binding S100 proteins show preferential heterodimerization. FEBS J. 2019;286:1859–1876.
    doi: 10.1111/febs.14775pubmed: 30719832google scholar: lookup
  29. Foell D., Roth J.. Proinflammatory S100 proteins in arthritis and autoimmune disease. Arthritis Rheum. 2004;50:3762–3771.
    doi: 10.1002/art.20631pubmed: 15593206google scholar: lookup
  30. Bresnick A.R., Weber D.J., Zimmer D.B.. S100 proteins in cancer. Nat. Rev. Cancer 2015;15:96–109.
    doi: 10.1038/nrc3893pmc: PMC4369764pubmed: 25614008google scholar: lookup
  31. Cristóvão J.S., Gomes C.M.. S100 Proteins in Alzheimer’s Disease. Front. Neurosci. 2019;13:463.
    doi: 10.3389/fnins.2019.00463pmc: PMC6532343pubmed: 31156365google scholar: lookup
  32. Sejersen K., Eriksson M.B., Larsson A.O.. Calprotectin as a Biomarker for Infectious Diseases: A Comparative Review with Conventional Inflammatory Markers. Int. J. Mol. Sci. 2025;26:6476.
    doi: 10.3390/ijms26136476pmc: PMC12249643pubmed: 40650251google scholar: lookup
  33. Garcia V., Perera Y.R., Chazin W.J.. A Structural Perspective on Calprotectin as a Ligand of Receptors Mediating Inflammation and Potential Drug Target. Biomolecules 2022;12:519.
    doi: 10.3390/biom12040519pmc: PMC9026754pubmed: 35454108google scholar: lookup
  34. Kawai T., Akira S.. Signaling to NF-kB by Toll-like receptors. Trends Mol. Med. 2007;13:460–469.
    doi: 10.1016/j.molmed.2007.09.002pubmed: 18029230google scholar: lookup
  35. Tóbon-Velasco J.C., Cuevas E., Torres-Ramos M.A.. Receptor for AGEs (RAGE) as mediator of NF-kB pathway activation in neuroinflammation and oxidative stress. CNS Neurol. Disord.-Drug Targets 2014;13:1615–1626.
    doi: 10.2174/1871527313666140806144831pubmed: 25106630google scholar: lookup
  36. Evers T.M.J., Sheikhhassani V., Haks M.C., Storm C., Ottenhoff T.H.M., Mashaghi A.. Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics. iScience 2022;25:103555.
    doi: 10.1016/j.isci.2021.103555pmc: PMC8693412pubmed: 34988399google scholar: lookup
  37. Cheng C.-C., Chang J., Ho A.-S., Sie Z.-L., Peng C.-L., Wang C.L., Dev K., Chang C.-C.. Tumor-intrinsic IFNα and CXCL10 are critical for immunotherapeutic efficacy by recruiting and activating T lymphocytes in tumor microenvironment. Cancer Immunol. Immunother. 2024;73:175.
    doi: 10.1007/s00262-024-03761-ypmc: PMC11219622pubmed: 38953994google scholar: lookup
  38. Karin N., Razon H.. Chemokines beyond chemo-attraction: CXCL10 and its significant role in cancer and autoimmunity. Cytokine 2018;109:24–28.
    doi: 10.1016/j.cyto.2018.02.012pubmed: 29449068google scholar: lookup
  39. Lye P., Dunk C.E., Zhang J., Wei Y., Nakpu J., Hamada H., Imperio G.E., Bloise E., Matthews S.G., Lye S.J.. ACE2 Is Expressed in Immune Cells That Infiltrate the Placenta in Infection-Associated Preterm Birth. Cells 2021;10:1724.
    doi: 10.3390/cells10071724pmc: PMC8303980pubmed: 34359894google scholar: lookup
  40. Andoh K., Nishimori A., Sakumoto R., Hayashi K.G., Hatama S.. The chemokines CCL2 and CXCL10 produced by bovine endometrial epithelial cells induce migration of bovine B lymphocytes, contributing to transuterine transmission of BLV infection. Vet. Microbiol. 2020;242:108598.
    doi: 10.1016/j.vetmic.2020.108598pubmed: 32122602google scholar: lookup
  41. Tanir H.M., Sener T., Artan S., Kaytaz B., Sahin-Mutlu F., Ozen M.E.. Programmed cell death (apoptosis) in placentas from normal pregnancy and pregnancy complicated by term (t) and preterm (p) premature rupture of membranes (PROM). Arch. Gynecol. Obstet. 2005;273:98–103.
    doi: 10.1007/s00404-005-0028-8pubmed: 16001193google scholar: lookup
  42. Akram K.M., Frost L.I., Anumba D.O.. Impaired autophagy with augmented apoptosis in a Th1/Th2-imbalanced placental micromilieu is associated with spontaneous preterm birth. Front. Mol. Biosci. 2022;9:897228.
    doi: 10.3389/fmolb.2022.897228pmc: PMC9460763pubmed: 36090032google scholar: lookup
  43. Sharp A.N., Heazell A.E., Crocker I.P., Mor G.. Placental apoptosis in health and disease. Am. J. Reprod. Immunol. 2010;64:159–169.
    doi: 10.1111/j.1600-0897.2010.00837.xpmc: PMC3025811pubmed: 20367628google scholar: lookup
  44. Lestari B., Fukushima T., Utomo R.Y., Wahyuningsih M.S.H.. Apoptotic and non-apoptotic roles of caspases in placenta physiology and pathology. Placenta 2024;151:37–47.
    doi: 10.1016/j.placenta.2024.03.013pubmed: 38703713google scholar: lookup
  45. Garcia-Lopez G., Vadillo-Ortega F., Merchant-Larios H., Maida-Claros R., Osorio M., Soriano-Becerril D., Flores-Herrera H., Beltran-Montoya J., Garfias-Becerra Y., Zaga-Clavellina V.. Evidence of in vitro differential secretion of 72 and 92 kDa type IV collagenases after selective exposure to lipopolysaccharide in human fetal membranes. Mol. Hum. Reprod. 2007;13:409–418.
    doi: 10.1093/molehr/gam025pubmed: 17449536google scholar: lookup
  46. Xu P., Alfaidy N., Challis J.R.. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor. J. Clin. Endocrinol. Metab. 2002;87:1353–1361.
    doi: 10.1210/jcem.87.3.8320pubmed: 11889208google scholar: lookup
  47. Sundrani D.P., Chavan-Gautam P.M., Pisal H.R., Mehendale S.S., Joshi S.R.. Matrix metalloproteinase-1 and -9 in human placenta during spontaneous vaginal delivery and caesarean sectioning in preterm pregnancy. PLoS ONE 2012;7:e29855.
    doi: 10.1371/journal.pone.0029855pmc: PMC3257231pubmed: 22253805google scholar: lookup
  48. Sahay A.S., Jadhav A.T., Sundrani D.P., Wagh G.N., Mehendale S.S., Joshi S.R.. Matrix metalloproteinases-2 (MMP-2) and matrix metalloproteinases -9 (MMP-9) are differentially expressed in different regions of normal and preeclampsia placentae. J. Cell Biochem. 2018;119:6657–6664.
    doi: 10.1002/jcb.26849pubmed: 29665148google scholar: lookup
  49. Schiopu A., Cotoi O.S.. S100A8 and S100A9: DAMPs at the crossroads between innate immunity, traditional risk factors, and cardiovascular disease. Mediat. Inflamm. 2013;2013:828354.
    doi: 10.1155/2013/828354pmc: PMC3881579pubmed: 24453429google scholar: lookup
  50. Donato R., Cannon B.R., Sorci G., Riuzzi F., Hsu K., Weber D.J., Geczy C.L.. Functions of S100 proteins. Curr. Mol. Med. 2013;13:24–57.
    doi: 10.2174/156652413804486214pmc: PMC3707951pubmed: 22834835google scholar: lookup
  51. Murase H., El-Sheikh Ali H., Ruby R.E., Scoggin K.E., Ball B.A.. Transcriptomic analysis of the chorioallantois in equine premature placental separation. Equine Vet. J. 2023;55:405–418.
    doi: 10.1111/evj.13602pubmed: 35622344google scholar: lookup
  52. Fedorka C.E., Ball B.A., Scoggin K.E., Loux S.C., Troedsson M.H.T., Adams A.A.. The feto-maternal immune response to equine placentitis. Am. J. Reprod. Immunol. 2019;82:e13179.
    doi: 10.1111/aji.13179pubmed: 31373743google scholar: lookup
  53. El-Sheikh Ali H., Dini P., Scoggin K., Loux S., Fedorka C., Boakari Y., Norris J., Esteller-Vico A., Kalbfleisch T., Ball B.. Transcriptomic analysis of equine placenta reveals key regulators and pathways involved in ascending placentitis†. Biol. Reprod. 2021;104:638–656.
    doi: 10.1093/biolre/ioaa209pubmed: 33345276google scholar: lookup
  54. Renaudin C.D., Troedsson M.H., Gillis C.L., King V.L., Bodena A.. Ultrasonographic evaluation of the equine placenta by transrectal and transabdominal approach in the normal pregnant mare. Theriogenology 1997;47:559–573.
    doi: 10.1016/S0093-691X(97)00014-9pubmed: 16728008google scholar: lookup
  55. Cima G.. Providing a humane death: Expanded euthanasia guidelines add species, process, technique considerations. J. Am. Vet. Med. Assoc. 2013;242:714–716.
    pubmed: 23445278
  56. El-Sheikh Ali H., Legacki E.L., Loux S.C., Esteller-Vico A., Dini P., Scoggin K.E., Conley A.J., Stanley S.D., Ball B.A.. Equine placentitis is associated with a downregulation in myometrial progestin signaling†. Biol. Reprod. 2019;101:162–176.
    doi: 10.1093/biolre/ioz059pubmed: 31107530google scholar: lookup
  57. El-Sheikh Ali H., Loux S.C., Kennedy L., Scoggin K.E., Dini P., Fedorka C.E., Kalbfleisch T.S., Esteller-Vico A., Horohov D.W., Erol E.. Transcriptomic analysis of equine chorioallantois reveals immune networks and molecular mechanisms involved in nocardioform placentitis. Vet. Res. 2021;52:103.
    doi: 10.1186/s13567-021-00972-4pmc: PMC8268225pubmed: 34238364google scholar: lookup
  58. Dobin A., Gingeras T.R.. Mapping RNA-seq Reads with STAR. Curr. Protoc. Bioinform. 2015;51:11.14.1–11.14.19.
    doi: 10.1002/0471250953.bi1114s51pmc: PMC4631051pubmed: 26334920google scholar: lookup
  59. Trapnell C., Roberts A., Goff L., Pertea G., Kim D., Kelley D.R., Pimentel H., Salzberg S.L., Rinn J.L., Pachter L.. Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks. Nat. Protoc. 2012;7:562–578.
    doi: 10.1038/nprot.2012.016pmc: PMC3334321pubmed: 22383036google scholar: lookup
  60. El-Sheikh Ali H., Legacki E.L., Scoggin K.E., Loux S.C., Dini P., Esteller-Vico A., Conley A.J., Stanley S.D., Ball B.A.. Steroid synthesis and metabolism in the equine placenta during placentitis. Reproduction 2020;159:289–302.
    doi: 10.1530/REP-19-0420pubmed: 31990666google scholar: lookup
  61. Legacki E.L., Corbin C.J., Ball B.A., Scoggin K.E., Stanley S.D., Conley A.J.. Steroidogenic enzyme activities in the pre- and post-parturient equine placenta. Reproduction 2018;155:51–59.
    doi: 10.1530/REP-17-0472pubmed: 29066529google scholar: lookup
  62. El-Sheikh Ali H., Scoggin K.E., Ruby R., Loynachan A., Boakari Y., Fernandes C., Dini P., Fedorka C.E., Loux S.C., Esteller-Vico A.. Equine cervical remodeling during placentitis and the prepartum period: A transcriptomic approach. Reproduction 2021;161:603–621.
    doi: 10.1530/REP-21-0008pubmed: 33780349google scholar: lookup
  63. Marchio S.P., El-Sheikh Ali H., Scott M.A., Barbosa Fernandes C., Scoggin K.E., Troedsson M., Boakari Y.. Decoding the amniotic membrane transcriptome during equine ascending placentitis. Sci. Rep. 2025;15:30714.
    doi: 10.1038/s41598-025-16671-5pmc: PMC12371064pubmed: 40841585google scholar: lookup
  64. Schmittgen T.D., Livak K.J.. Analyzing real-time PCR data by the comparative C(T) method. Nat. Protoc. 2008;3:1101–1108.
    doi: 10.1038/nprot.2008.73pubmed: 18546601google scholar: lookup
  65. Chatterjee A., Ahn A., Rodger E.J., Stockwell P.A., Eccles M.R.. A Guide for Designing and Analyzing RNA-Seq Data. .
    pubmed: 29767357

Citations

This article has been cited 0 times.
Subscribe to our newsletter
Join 99,928 horse owners like you who receive our email updates on horse health and nutrition.