Short title: Lgals9 splice variants during early gestation

Disruption of fetal‐maternal tolerance mechanisms can contribute to pregnancy complications, including spontaneous abortion. Galectin‐9 (LGALS9), a tandem repeat lectin, associated with immunomodulation is expressed in the endometrium during the mid‐ and late‐secretory phases and in early‐pregnancy decidua. However, the role of LGALS9 during pregnancy remains poorly understood. We used qPCR and immu nohistochemical staining to analyze the expression of 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 of which the expression 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 IFNG production by decidual NK cells. In human patients, six Lgals9 splice variants were detected and a decrease in Lgals9 D5/10 was associated with spontaneous abortion. Altogether, these resu lts show a differential regulation of Lgals9 isoforms expression during normal and pathological pregnancies and designate Lgals9 as a potential marker for adverse pregnancy outcomes. Summary sentence: Differential regulation of Lgals9 isoforms expression during normal and pathological pregnancies designates Lgals9 profile as a potential marker for adverse pregnancy outcomes.