{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:48:31Z","timestamp":1790182111153,"version":"4.1.0"},"reference-count":84,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100015103","name":"Japan Racing Association","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015103","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Recently, we reported that sperm induce cluster of differentiation 44 (CD44) expression and Toll-like receptor 2 (TLR2)-mediated inflammatory response in bovine uterus. In the present study, we hypothesized that the interaction between CD44 of bovine endometrial epithelial cells (BEECs) and hyaluronan (HA) affects sperm attachment and thereby enhancing TLR2-mediated inflammation. To test our hypothesis, at first, <jats:italic>in-silico<\/jats:italic> approaches were employed to define the binding affinity of HA for CD44 and TLR2. Further, an <jats:italic>in-vitro<\/jats:italic> experiment using the sperm-BEECs co-culture model was applied to investigate the effect of HA on sperm attachment and inflammatory response. Here, low molecular weight (LMW) HA at different concentrations (0, 0.1, 1, or 10 \u00b5g\/mL) was incubated with BEECs for 2 h followed by the co-culture without- or with non-capacitated washed sperm (10<jats:sup>6<\/jats:sup>\/ml) for additional 3 h was performed. The present in-silico model clarified that CD44 is a high-affinity receptor for HA. Moreover, TLR2 interactions with HA oligomer (4- and 8-mers) target a different subdomain (h-bonds) compared to TLR2-agonist (PAM3) which targets a central hydrophobic pocket. However, the interaction of LMW HA (32-mers) with TLR2 revealed no stability of HA at any pocket of TLR2. Notably, the immunofluorescence analysis revealed the HA localization in both endometrial stroma and epithelia of <jats:italic>ex-vivo<\/jats:italic> endometrial explant. Moreover, ELISA showed significant levels of HA in BEECs culture media. Importantly, BEECs pretreatment with HA prior to sperm exposure increased the number of attached sperm to BEECs, and upregulated the transcriptional levels of pro-inflammatory genes (<jats:italic>TNFA, IL-1B, IL-8, and PGES<\/jats:italic>) in BEECs in response to sperm. However, BEECs treated with HA only (no sperm exposure) did not show any significant effect on the transcript abundance of pro-inflammatory genes when compared to the non-treated BEECs. Altogether, our findings strongly suggest a possible cross-talk between sperm and endometrial epithelial cells <jats:italic>via<\/jats:italic> HA and HA binding receptors (CD44 and TLR2) to induce a pro-inflammatory response in bovine uterus.<\/jats:p>","DOI":"10.3389\/fendo.2023.1134868","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T19:49:19Z","timestamp":1683748159000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Hyaluronan regulates sperm-induced inflammatory response by enhancing sperm attachment to bovine endometrial epithelial cells via CD44: in-silico and in-vitro approaches"],"prefix":"10.3389","volume":"14","author":[{"given":"Mohamed Aboul","family":"Ezz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Mansouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ihshan","family":"Akthar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Samy","family":"Yousef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rasoul","family":"Kowsar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akio","family":"Miyamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/S0378-4320(02)00230-0","article-title":"Influence of pre-ovulatory insemination and early pregnancy on the infiltration by cells of the immune system in the sow endometrium","volume":"75","author":"Kaeoket","year":"2003","journal-title":"Anim Reprod Sci"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.148.6.1699","article-title":"Activation and distribution of inflammatory cells in the mouse uterus during the preimplantation period","volume":"148","author":"McMaster","year":"1992","journal-title":"J Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1530\/rep.1.00160","article-title":"Seminal plasma regulates endometrial cytokine expression, leukocyte recruitment and embryo development in the pig","volume":"128","author":"O\u2019Leary","year":"2004","journal-title":"Reproduction"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1071\/rd09012","article-title":"Spermatozoa and seminal plasma induce a greater inflammatory response in the ovine uterus at oestrus than dioestrus","volume":"21","author":"Scott","year":"2009","journal-title":"Reprod Fertil Dev"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1992.tb00765.x","article-title":"The leukocytic reaction of the human uterine cervix","volume":"28","author":"Thompson","year":"1992","journal-title":"Am J Reprod Immunol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21041432","article-title":"Persistent breeding-induced endometritis in mares - a multifaceted challenge: from clinical aspects to immunopathogenesis and pathobiology","volume":"21","author":"Canisso","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B7","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1111\/j.1439-0531.2012.02120.x","article-title":"Post-mating inflammatory responses of the uterus","author":"Katila","year":"2012","journal-title":"Reprod Domest Anim"},{"key":"B8","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1111\/j.1439-0531.2011.01850.x","article-title":"The immunology of early pregnancy in farm animals","author":"Hansen","year":"2011","journal-title":"Reprod Domest Anim"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1530\/ror.0.0050164","article-title":"Control of the immunological environment of the uterus","volume":"5","author":"Robertson","year":"2000","journal-title":"Rev Reprod"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gap095","article-title":"Novel pathways for implantation and establishment and maintenance of pregnancy in mammals","volume":"16","author":"Bazer","year":"2010","journal-title":"Mol Hum Reprod"},{"key":"B11","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/s0165-0378(02)00019-0","article-title":"The innate and early immune response to pathogen challenge in the female genital tract and the pivotal role of epithelial cells","volume":"57","author":"Quayle","year":"2002","journal-title":"J Reprod Immunol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1146\/annurev.immunol.20.083001.084359","article-title":"Innate immune recognition","volume":"20","author":"Janeway","year":"2002","journal-title":"Annu Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1177\/1933719108316391","article-title":"Expression and function of toll-like receptors at the maternal-fetal interface","volume":"15","author":"Koga","year":"2008","journal-title":"Reprod Sci"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0214516","article-title":"TLR2\/4 signaling pathway mediates sperm-induced inflammation in bovine endometrial epithelial cells in vitro","volume":"14","author":"Ezz","year":"2019","journal-title":"PloS One"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1530\/REP-19-0414","article-title":"Sperm enter glands of preovulatory bovine endometrial explants and initiate inflammation","volume":"159","author":"Akthar","year":"2020","journal-title":"Reproduction"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.1209775","article-title":"Endogenous ligands of TLR2 and TLR4: agonists or assistants","volume":"87","author":"Erridge","year":"2010","journal-title":"J Leukoc Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/714081","article-title":"Hyaluronan is not a ligand but a regulator of toll-like receptor signaling in mesangial cells: role of extracellular matrix in innate immunity","volume":"2014","author":"Ebid","year":"2014","journal-title":"ISRN Nephrol"},{"key":"B18","doi-asserted-by":"publisher","first-page":"R43","DOI":"10.1530\/rep-16-0240","article-title":"Regulation and roles of the hyaluronan system in mammalian reproduction","volume":"153","author":"Fouladi-Nashta","year":"2017","journal-title":"Reproduction"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1071\/rd11152","article-title":"Glycosaminoglycans in the accessory sex glands, testes and seminal plasma of alpaca and ram","volume":"24","author":"Kershaw-Young","year":"2012","journal-title":"Reprod Fertil Dev"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1071\/rd00034","article-title":"Localization and quantitation of hyaluronan and sulfated glycosaminoglycans in the tissues and intraluminal fluid of the pig oviduct","volume":"12","author":"Tienthai","year":"2000","journal-title":"Reprod Fertil Dev"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2008.07.005","article-title":"Concentration and distribution of hyaluronic acid in mouse uterus throughout the estrous cycle","volume":"92","author":"Teixeira Gomes","year":"2009","journal-title":"Fertil Steril"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1530\/rep-09-0424","article-title":"Hyaluronan (HA) content, the ratio of HA fragments and the expression of CD44 in the ovine cervix vary with the stage of the oestrous cycle","volume":"140","author":"Perry","year":"2010","journal-title":"Reproduction"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod66.3.707","article-title":"Expression of hyaluronan synthases and CD44 messenger RNAs in porcine cumulus-oocyte complexes during In vitro Maturation1","volume":"66","author":"Kimura","year":"2002","journal-title":"Biol Reprod"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.102.011577","article-title":"Expression of hyaluronan synthases and corresponding hyaluronan receptors is differentially regulated during oocyte maturation in Cattle1","volume":"69","author":"Schoenfelder","year":"2003","journal-title":"Biol Reprod"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1071\/rd14294","article-title":"Localisation and endocrine control of hyaluronan synthase (HAS) 2, HAS3 and CD44 expression in sheep granulosa cells","volume":"28","author":"Chavoshinejad","year":"2016","journal-title":"Reprod Fertil Dev"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)80077-1","article-title":"Synthesis and accumulation of hyaluronic acid and proteoglycans in the mouse cumulus cell-oocyte complex during follicle-stimulating hormone-induced mucification","volume":"264","author":"Salustri","year":"1989","journal-title":"J Biol Chem"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1242\/dev.020461","article-title":"Hyaluronan fragments generated by sperm-secreted hyaluronidase stimulate cytokine\/chemokine production via the TLR2 and TLR4 pathway in cumulus cells of ovulated COCs, which may enhance fertilization","volume":"135","author":"Shimada","year":"2008","journal-title":"Development"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/12.5.1080","article-title":"The role of hyaluronic acid as a mediator and regulator of cervical ripening","volume":"12","author":"El Maradny","year":"1997","journal-title":"Hum Reprod"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00101","article-title":"Hyaluronan, a crucial regulator of inflammation","volume":"5","author":"Petrey","year":"2014","journal-title":"Front Immunol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1172\/jci119054","article-title":"Hyaluronan (HA) fragments induce chemokine gene expression in alveolar macrophages. the role of HA size and CD44","volume":"98","author":"McKee","year":"1996","journal-title":"J Clin Invest"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.4.1863","article-title":"Oligosaccharides of hyaluronan are potent activators of dendritic cells","volume":"165","author":"Termeer","year":"2000","journal-title":"J Immunol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1681\/asn.V9122283","article-title":"Hyaluronan induces monocyte chemoattractant protein-1 expression in renal tubular epithelial cells","volume":"9","author":"Beck-Schimmer","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"B33","article-title":"Synergistic effect of hyaluronan oligosaccharides and vascular endothelial growth factor on angiogenesis","volume":"75","author":"Montesano","year":"1996","journal-title":"vitro. Lab Invest"},{"key":"B34","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1165\/rcmb.2002-0167OC","article-title":"Low molecular weight hyaluronan from stretched lung enhances interleukin-8 expression","volume":"30","author":"Mascarenhas","year":"2004","journal-title":"Am J Respir Cell Mol Biol"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/2087204","article-title":"The importance of CD44 as a stem cell biomarker and therapeutic target in cancer","volume":"2016","author":"Thapa","year":"2016","journal-title":"Stem Cells Int"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00068","article-title":"Interactions between CD44 and hyaluronan in leukocyte trafficking","volume":"6","author":"McDonald","year":"2015","journal-title":"Front Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00201","article-title":"Interactions between hyaluronan and its receptors (CD44, RHAMM) regulate the activities of inflammation and cancer","volume":"6","author":"Misra","year":"2015","journal-title":"Front Immunol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90337-9","article-title":"Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm","volume":"76","author":"Springer","year":"1994","journal-title":"Cell"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1084\/jem.183.3.1119","article-title":"CD44 and its ligand hyaluronate mediate rolling under physiologic flow: a novel lymphocyte-endothelial cell primary adhesion pathway","volume":"183","author":"DeGrendele","year":"1996","journal-title":"J Exp Med"},{"key":"B40","doi-asserted-by":"publisher","first-page":"185","DOI":"10.3109\/08820139909061147","article-title":"CD3-mediated T cell activation is inhibited by anti-CD44 monoclonal antibodies directed to the hyaluronan-binding region","volume":"28","author":"Sugiyama","year":"1999","journal-title":"Immunol Invest"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.143.8.2457","article-title":"Dual role of the CD44 molecule in T cell adhesion and activation","volume":"143","author":"Shimizu","year":"1989","journal-title":"J Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.5.2492","article-title":"Induction of IL-12 and chemokines by hyaluronan requires adhesion-dependent priming of resident but not elicited macrophages","volume":"159","author":"Hodge-Dufour","year":"1997","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"7","DOI":"10.4049\/jimmunol.144.1.7","article-title":"Antibodies against the CD44 p80, lymphocyte homing receptor molecule augment human peripheral blood T cell activation","volume":"144","author":"Denning","year":"1990","journal-title":"J Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.7.4171","article-title":"Induction and regulation of macrophage metalloelastase by hyaluronan fragments in mouse macrophages","volume":"162","author":"Horton","year":"1999","journal-title":"J Immunol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.619408","article-title":"Peptidoglycan switches off the TLR2-mediated sperm recognition and triggers sperm localization in the bovine endometrium","volume":"11","author":"Elesh","year":"2020","journal-title":"Front Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki524","article-title":"TM-align: a protein structure alignment algorithm based on the TM-score","volume":"33","author":"Zhang","year":"2005","journal-title":"Nucleic Acids Res"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1005663","article-title":"Atomistic fingerprint of hyaluronan\u2013CD44 binding","volume":"13","author":"Vuorio","year":"2017","journal-title":"PloS Comput Biol"},{"key":"B48","article-title":"Interation between CD44 and HA16: an investigation on multiple binding modes of the complex by using molecular dynamics simulation studies","volume":"96","author":"Paul","year":"2019","journal-title":"J Indian Chem Soc"},{"key":"B49","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/0010-4655(95)00042-E","article-title":"GROMACS: a message-passing parallel molecular dynamics implementation","volume":"91","author":"Berendsen","year":"1995","journal-title":"Comput Phys Commun"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1021\/ct900549r","article-title":"Implementation of the CHARMM force field in GROMACS: analysis of protein stability effects from correction maps, virtual interaction sites, and water models","volume":"6","author":"Bjelkmar","year":"2010","journal-title":"J Chem Theory Comput"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21287","article-title":"CHARMM: the biomolecular simulation program","volume":"30","author":"Brooks","year":"2009","journal-title":"J Comput Chem"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21816","article-title":"SwissParam: a fast force field generation tool for small organic molecules","volume":"32","author":"Zoete","year":"2011","journal-title":"J Comput Chem"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.21334","article-title":"AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"Trott","year":"2010","journal-title":"J Comput Chem"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1021\/ci500020m","article-title":"G_mmpbsa\u2013a GROMACS tool for high-throughput MM-PBSA calculations","volume":"54","author":"Kumari","year":"2014","journal-title":"J Chem Inf Model"},{"key":"B55","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.jmgm.2016.01.003","article-title":"Molecular dynamics simulation of non-covalent single-walled carbon nanotube functionalization with surfactant peptides","volume":"64","author":"Barzegar","year":"2016","journal-title":"J Mol Graph Model"},{"key":"B56","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1016\/j.jmgm.2017.02.016","article-title":"Designing new surfactant peptides for binding to carbon nanotubes via computational approaches","volume":"74","author":"Mansouri","year":"2017","journal-title":"J Mol Graph Model"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.1016\/s0093-691x(98)00011-9","article-title":"Local distributions of oviductal estradiol, progesterone, prostaglandins, oxytocin and endothelin-1 in the cyclic cow","volume":"49","author":"Wijayagunawardane","year":"1998","journal-title":"Theriogenology"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1177\/42.11.7523491","article-title":"Distribution of hyaluronan in bull reproductive organs","volume":"42","author":"Tammi","year":"1994","journal-title":"J Histochem Cytochem"},{"key":"B59","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.mce.2003.12.002","article-title":"Hyaluronan in the bovine oviduct\u2013modulation of synthases and receptors during the estrous cycle","volume":"214","author":"Ulbrich","year":"2004","journal-title":"Mol Cell Endocrinol"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod62.5.1116","article-title":"Production of prostaglandin f(2alpha) by cultured bovine endometrial cells in response to tumor necrosis factor alpha: cell type specificity and intracellular mechanisms","volume":"62","author":"Skarzynski","year":"2000","journal-title":"Biol Reprod"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1677\/joe-08-0237","article-title":"Regulation of prostaglandin biosynthesis by interleukin-1 in cultured bovine endometrial cells","volume":"199","author":"Tanikawa","year":"2008","journal-title":"J Endocrinol"},{"key":"B62","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1095\/biolreprod.108.075184","article-title":"Evidence for estrogen-dependent uterine serpin (SERPINA14) expression during estrus in the bovine endometrial glandular epithelium and lumen","volume":"81","author":"Ulbrich","year":"2009","journal-title":"Biol Reprod"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/0093-691x(94)90117-2","article-title":"Prostaglandin E2 levels in uterine tissues and its relationship with uterine and luteal progesterone during the estrous cycle in dairy cows","volume":"42","author":"Cerbito","year":"1994","journal-title":"Theriogenology"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.22955","article-title":"A proinflammatory response of bovine endometrial epithelial cells to active sperm","volume":"85","author":"Elweza","year":"2018","journal-title":"vitro. Mol Reprod Dev"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod38.5.1171","article-title":"Capacitation of bovine sperm by heparin","volume":"38","author":"Parrish","year":"1988","journal-title":"Biol Reprod"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1987.9999","article-title":"Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction","volume":"162","author":"Chomczynski","year":"1987","journal-title":"Anal Biochem"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0162309","article-title":"Sperm binding to oviduct epithelial cells enhances TGFB1 and IL10 expressions in epithelial cells as well as neutrophils In vitro: prostaglandin E2 as a main regulator of anti-inflammatory response in the bovine oviduct","volume":"11","author":"Yousef","year":"2016","journal-title":"PloS One"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1093\/protein\/8.2.127","article-title":"LIGPLOT: a program to generate schematic diagrams of protein-ligand interactions","volume":"8","author":"Wallace","year":"1995","journal-title":"Protein Eng"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1071\/rd21265","article-title":"Sperm interaction with the uterine innate immune system: toll-like receptor 2 (TLR2) is a main sensor in cattle","volume":"34","author":"Akthar","year":"2021","journal-title":"Reprod Fertil Dev"},{"key":"B71","doi-asserted-by":"publisher","first-page":"S88","DOI":"10.1093\/jas\/skaa147","article-title":"Sensing sperm via maternal immune system: a potential mechanism for controlling microenvironment for fertility in the cow","volume":"98","author":"Marey","year":"2020","journal-title":"J Anim Sci"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.09.008","article-title":"Crystal structure of the TLR1-TLR2 heterodimer induced by binding of a tri-acylated lipopeptide","volume":"130","author":"Jin","year":"2007","journal-title":"Cell"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.0c05502","article-title":"Molecular dynamics simulation study on allosteric regulation of CD44-hyaluronan binding as a force sensing mechanism","volume":"6","author":"Lintuluoto","year":"2021","journal-title":"ACS Omega"},{"key":"B74","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1530\/rep-13-0001","article-title":"Regulation of the hyaluronan system in ovine endometrium by ovarian steroids","volume":"145","author":"Raheem","year":"2013","journal-title":"Reproduction"},{"key":"B75","doi-asserted-by":"publisher","DOI":"10.1016\/s0015-0282(02)03230-2","article-title":"Human sperm cells express CD44","volume":"78","author":"Bains","year":"2002","journal-title":"Fertil Steril"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1136\/ard.54.5.429","article-title":"Functions of hyaluronan","volume":"54","author":"Laurent","year":"1995","journal-title":"Ann Rheum Dis"},{"key":"B77","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1046\/j.1365-2796.1997.00170.x","article-title":"Hyaluronan: its nature, distribution, functions and turnover","volume":"242","author":"Fraser","year":"1997","journal-title":"J Intern Med"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.52.35088","article-title":"Hyaluronan fragments synergize with interferon-gamma to induce the c-X-C chemokines mig and interferon-inducible protein-10 in mouse macrophages","volume":"273","author":"Horton","year":"1998","journal-title":"J Biol Chem"},{"key":"B79","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.12.8013","article-title":"Hyaluronan fragments induce nitric-oxide synthase in murine macrophages through a nuclear factor kappaB-dependent mechanism","volume":"272","author":"McKee","year":"1997","journal-title":"J Biol Chem"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2006.01537.x","article-title":"The role of hyaluronan degradation products as innate alloimmune agonists","volume":"6","author":"Tesar","year":"2006","journal-title":"Am J Transplant"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.2.1272","article-title":"Hyaluronan fragments act as an endogenous danger signal by engaging TLR2","volume":"177","author":"Scheibner","year":"2006","journal-title":"J Immunol"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1700713","article-title":"Role of CD44 in regulating TLR2 activation of human macrophages and downstream expression of proinflammatory cytokines","volume":"200","author":"Qadri","year":"2018","journal-title":"J Immun"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.6.4235","article-title":"CD44 suppresses TLR-mediated inflammation","volume":"180","author":"Kawana","year":"2008","journal-title":"J Immun"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202202118","article-title":"Hyaluronan receptors as mediators and modulators of the tumor microenvironment","volume":"12","author":"Carvalho","year":"2022","journal-title":"Adv Healthc Mater"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1134868\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T19:49:26Z","timestamp":1683748166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1134868\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":84,"alternative-id":["10.3389\/fendo.2023.1134868"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1134868","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"article-number":"1134868"}}