JAK/STAT signaling pathway in the spleen and liver during early pregnancy in ewes

Pregnancy induces adaptations in the maternal immune system, including the liver and spleen, in a gestation-dependent manner. The Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway participates in immune tolerance at the maternal-fetal interface. Nevertheless, whether pregnancy affects the JAK/STAT signaling pathway in the liver and spleen of ewes has remained unclear. In this study, samples of ovine liver and spleen were collected at day 16 of the estrous cycle and at days 13, 16, 25, and 70 of gestation (n = 6 for each group). The expression of JAK/STAT members, including interferon α/β receptor 1 (IFNAR1), JAK1, tyrosine kinase 2 (TYK2), STAT3, interferon regulatory factor 9 (IRF9), B-cell lymphoma-extra large (BCL-XL), BCL-2, myelocytomatosis viral oncogene homolog (c-Myc), and P21 (a protein with a molecular weight of 21 kDa), was analyzed using RT-qPCR, western blotting, and immunohistochemistry. The results revealed that pregnancy enhanced the expression of IFNAR1, JAK1, TYK2, BCL-2, and P21 in the liver and IFNAR1 and P21 in the spleen, but inhibited the expression of STAT3 and BCL-XL in the liver, and JAK1, TYK2, STAT3, IRF9, and BCL-XL in the spleen. In addition, the expression of c-Myc and IRF9 in the liver, and c-Myc and BCL-2 in the spleen was modulated in a pregnancy-stage-specific manner. In summary, pregnancy modulated the expression of JAK/STAT members in maternal liver and spleen in a pregnancy-stage- and tissue-specific manner, which may contribute to the maternal immunotolerance and increases of spleen and liver sizes during gestation.