title: Definitive class I human leukocyte antigen expression in gestational placentation: HLA-F, HLA-E, HLA-C, and HLA-G in extravillous trophoblast invasion on placentation, pregnancy, and parturition.
abstract: The extravillous trophoblasts (EVT) express HLA-C and HLA-G, but HLA-E and HLA-F are the subject of conflicting reports. In this study, we define the HLA expression profile during active EVT placental implantation, pregnancy development, and parturition.
  
  
  
  Immunohistochemistry, q-PCR, and Western blot were used to investigate HLA-C, HLA-E, and HLA-F placental expression across gestation from the early first trimester, late first trimester, second trimester (n=10 in each), preterm gestation (n=6) to elective term cesarean section and term vaginal deliveries (n=12, 38-41 weeks). EVT explants and Swan71 cells were used to assess HLA-C and HLA-F during active EVT migration.
  
  
  
  HLA-G, HLA-C, and HLA-F were expressed by 1st-trimester EVT and became intracellular and weaker as gestation progressed. HLA-E was only expressed in 1st-trimester placenta. HLA-F and HLA-C mRNA and protein expression levels showed a significant increase in the fetal villous mesenchyme across gestation. HLA-C levels increased with labor. We detected a 100-kDa HLA-F band in early pregnancy suggesting dimer formation on the EVT surface. These results were confirmed in EVT outgrowths and Swan71 trophoblast which showed that HLA-F and HLA-G are increased on the cell surface of migrating EVT, while HLA-C was internalized.
  
  
  
  Expression of HLA-F and HLA-G on the cell surface of actively migrating EVT supports their specific role in early EVT invasion and interactions with uterine natural killer cells. HLA-C's limited expression to the proliferative EVT suggests a protective role in the earliest events of implantation but not in active EVT invasion. We also show for the first time that HLA-C may be involved in parturition.
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada.|Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.|Division of MFM Obstetrics and Gynecology, OHSU, Portland, Oregon, USA.
authors.forename: Rinat
authors.initials: R
authors.lastname: Hackmon
authors.affiliation: Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Lakmini
authors.initials: L
authors.lastname: Pinnaduwage
authors.affiliation: Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.|Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lye
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Geraghty
authors.affiliation: Department of Obstetrics and Gynecology, University of Toronto, Mount Sinai Hospital, Toronto, ON, Canada.|Lunenfeld Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Caroline E
authors.identifier: 0000-0002-4146-099X
authors.initials: CE
authors.lastname: Dunk
mesh_terms: D000328:Adult; D002465:Cell Movement; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D036801:Parturition / Q000378:metabolism; D010920:Placenta / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy / Q000378:metabolism*; D011264:Pregnancy Trimesters / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014327:Trophoblasts / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015395:Histocompatibility Antigens Class I; D012333:RNA, Messenger
keywords: HLA-C; HLA-E; HLA-F; human leukocyte antigen; placenta; trophoblast