title: Profiling Lgals9 splice variant expression at the fetal-maternal interface: implications in normal and pathological human pregnancy.
abstract: Disruption of fetal-maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin-9 (LGALS9), a tandem repeat lectin associated with immune modulation, is expressed in the endometrium during the mid and late secretory phases and in decidua during human early pregnancy. However, the role of LGALS9 during pregnancy remains poorly understood. We used real-time PCR and immunohistochemical staining to analyze the expression of Lgals9/LGALS9 during mouse gestation as well as in human tissues obtained from normal pregnancy and spontaneous abortions. In mice, three Lgals9 splice variants were detected, the expression of which was differentially regulated during gestation. Furthermore, decidual Lgals9 expression was deregulated in a mouse model of spontaneous abortion, whereas placental levels did not change. We further found that the LGALS9 D5 isoform suppresses interferon gamma production by decidual natural killer cells. In human patients, six Lgals9 splice variants were detected, and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these results show a differential regulation of Lgals9 isoform expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes.
authors.affiliation: Departments of Radiation Oncology and Medical Oncology, Angiogenesis Laboratory, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Roy
authors.initials: R
authors.lastname: Heusschen
authors.forename: Nancy
authors.initials: N
authors.lastname: Freitag
authors.forename: Irene
authors.initials: I
authors.lastname: Tirado-González
authors.forename: Gabriela
authors.initials: G
authors.lastname: Barrientos
authors.forename: Petra
authors.initials: P
authors.lastname: Moschansky
authors.forename: Raquel
authors.initials: R
authors.lastname: Muñoz-Fernández
authors.forename: Ester
authors.initials: E
authors.lastname: Leno-Durán
authors.forename: Burghard F
authors.initials: BF
authors.lastname: Klapp
authors.forename: Victor L J L
authors.initials: VL
authors.lastname: Thijssen
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Blois
mesh_terms: D000022:Abortion, Spontaneous / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D005260:Female; D037161:Galectins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology*; D006801:Humans; D007694:Killer Cells, Natural; D008297:Male; D033261:Maternal-Fetal Relations / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D011247:Pregnancy; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D037161:Galectins; D020033:Protein Isoforms; C105032:LGALS9 protein, human; C508186:galectin 9, mouse