Impact of SOCS2 deficiency on cytokine profile in gestational diabetes and macrosomia

Abstract

Background and aims: The Suppressor of Cytokine Signalling 2 (SOCS2) modulates cytokine response, body growth, metabolism of lipids and carbohydrates, and inflammatory responses. We aim to investigate the serum cytokine profile during pregnancy in SOCS2-deficient mice, a model that develops Gestational Diabetes (GDM) and macrosomia. Materials and methods: The cytokine profile was analyzed using an array of 48-mouse cytokine panel which provides data from biomarkers related to inflammation and immune response. Fasting serum (1μL) was used to analyze cytokines in 4 Socs2-/- and 4 C57BI/6J (control) females at day 0 (basal), day 14 (gestation) and day 21 (postpartum) of pregnancy (OEBA_ULPGC 17/2024). Results were compared using Mann-Whitney’s U and Student’s tests. Results: Twenty-three out of 43 cytokines analyzed showed different expression profiles between groups and/or gestational times (Table 1). In the control mice, serum levels of 6 cytokines (IL-12, IL-5, Colony Stimulator Factor (CSF)3, Chemokine CXC Ligand (CXCL)1, CXCL-11 and Fibroblast Growth Factor (FGF)21) increased during pregnancy compared to baseline and the Socs2-/- mice. However, the profile of increased cytokines changed in the postpartum stage (IL-33, Tumor Necrosis Factor (TNF)-α, CXCL2, CXCL9, CCL-11, and Hepatocyte Growth Factor (HGF)). In baseline Socs2-/- mice, serum levels of 8 cytokines were elevated (IL-6, IL-17F, IL-22, IL-12, TNF-α, CSF3, CXCL2, and CXCL11), while 7 cytokines (IL-33, IL-9, CXCL9, CCL12, CCL11, HGF, and FGF21) were reduced. In pregnant Socs2-/- mice, the amount of cytokines levels further increased during gestation (Interferon (IFN)-α2, IL-1α, IL-17F, IL-33, IL-9, IL-22, IL-10, IL-16, IL-2, TNF- α, CXCL-2, CXCL-9, and CCL-12), whereas during postpartum several cytokines remained elevated or increased further (IL-6, IL-1α, IL-9, IL-17F, IL-10, IL-5, IL-16, CXCL9, CCL11, and HGF). Compared to controls(p<0.05), baseline Socs2-/- females showed higher CSF3 and lower CCL11 levels. During gestation, they exhibited higher levels of IFN-α2 and IL17F but lower levels of FGF21. Finally, in postpartum, serum levels of IL17F and IL12 were higher Socs2-/- mice. Conclusion: Pregnancy constitute a pro-inflammatory condition in both control and Socs2-/- mice. However, the absence of SOCS2 exacerbates this condition during pregnancy, potentially contributing to GDM and macrosomia. This heightened pro-inflammatory phenotype suggests that SOCS2 influence the normal cytokine balance during both gestation and postpartum. These findings support the hypothesis that SOCS2 may protect against pregnancy-related complications. Further studies with larger sample sizes will be assessed to confirm these preliminary findings.