title: Hematopoetic prostaglandin D synthase: an ESR1-dependent oviductal epithelial cell synthase.
abstract: Oviductal disease is a primary cause of infertility, a problem that largely stems from excessive inflammation of this key reproductive organ. Our poor understanding of the mechanisms regulating oviductal inflammation restricts our ability to diagnose, treat, and/or prevent oviductal disease. Using mice, our objective was to determine the spatial localization, regulatory mechanism, and functional attributes of a hypothesized regulator of oviductal inflammation, the hematopoietic form of prostaglandin D synthase (HPGDS). Immunohistochemistry revealed specific localization of HPGDS to the oviduct's epithelium. In the isthmus, expression of HPGDS was consistent. In the ampulla, expression of HPGDS appeared dependent upon stage of the estrous cycle. HPGDS was expressed in the epithelium of immature and cycling mice but not in the oviducts of estrogen receptor α knockouts. Two receptor subtypes bind PGD₂: PGD₂ receptor and G protein-coupled receptor 44. Expression of mRNA for Ptgdr was higher in the epithelial cells (EPI) than in the stroma (P < 0.05), whereas mRNA for Gpr44 was higher in the stroma than epithelium (P < 0.05). Treatment of human oviductal EPI with HQL-79, an inhibitor of HPGDS, decreased cell viability (P < 0.05). Treatment of mice with HQL-79 increased mRNA for chemokine (C-C motif) ligands 3, 4, and 19; chemokine (C-X-C motif) ligands 11 and 12; IL-13 and IL-17B; and TNF receptor superfamily, member 1b (P < 0.02 for each mRNA). Overall, these results suggest that HPGDS may play a role in the regulation of inflammation and EPI health within the oviduct.
authors.affiliation: Department of Animal and Food Sciences, University of Kentucky, Lexington, Kentucky 40546, USA. pbrid2@email.uky.edu
authors.forename: Phillip J
authors.initials: PJ
authors.lastname: Bridges
authors.forename: Myoungkun
authors.initials: M
authors.lastname: Jeoung
authors.forename: Sarah
authors.initials: S
authors.lastname: Shim
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Park
authors.forename: Jae Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Sapsford
authors.forename: Kourtney
authors.initials: K
authors.lastname: Trudgen
authors.forename: Chemyong
authors.initials: C
authors.lastname: Ko
authors.forename: Myung Chan
authors.initials: MC
authors.lastname: Gye
authors.forename: Misung
authors.initials: M
authors.lastname: Jo
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology*; D047628:Estrogen Receptor alpha / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology; D019746:Intramolecular Oxidoreductases; D007535:Isomerases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010057:Oviducts / Q000166:cytology / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism
chemical_list: C116322:4-benzhydryloxy-1-(3-(1H-tetrazol-5-yl-)-propyl)piperidine; D047628:Estrogen Receptor alpha; D010880:Piperidines; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D007535:Isomerases; D019746:Intramolecular Oxidoreductases; C545516:HPGDS protein, mouse; C036293:prostaglandin D2 receptor