The prevalence of maternal obesity is increasing rapidly worldwide and is reported as a major gynaecological problem, due to increased mother and child mortality and morbidity. It has been shown that while obese women have a 10% tendency to develop pregnancy complications such as gestational diabetes mellitus (GDM), their children also develop cardiovascular and metabolic diseases in later life.1 Maternal obesity and GDM may be associated with a chronic condition called “meta-inflammation” that develops against low-grade inflammation and an acute inflammatory response. Developing cardiovascular and metabolic disorders in addition to pregnancy complications such as pre-eclampsia, thromboembolism and gestational diabetes in obese women is one of the risks that obese women face during the process of their pregnancy.2 In this group, the risk of developing GDM was found to be 1.3–3.8 times higher in obese women compared to women with normal body mass index. It is also known that 70% of women with GDM have the risk of developing type 2 diabetes (T2DM).1, 3, 4, 5

GDM is defined as glucose intolerance that begins during the second or third trimester of pregnancy. Many experimental and clinical studies have proven that metabolic syndrome components such as impaired glucose tolerance, dyslipidaemia and hypertension are associated with low-grade systemic inflammation. Metabolic syndrome is a metabolic disorder characterised by biochemical and clinical findings in which some or all of the parameters of insulin resistance, impaired glucose balance, dyslipidaemia, obesity and hypertension are present.4 Inflammatory signalling pathways are activated in metabolic syndrome, changing the release of proinflammatory and anti-inflammatory cytokines, and causing biochemical and clinical disorders attributed to metabolic syndrome. Despite advances in this area, the pathogenesis and pathophysiology of GDM has not been fully clarified.1, 4, 6

It has been reported that proinflammatory and anti-inflammatory cytokines are necessary for the development and continuation of pregnancy from the beginning to the end of pregnancy.7 It has been shown that gestational diabetes mellitus constitutes a metabolic disorder that needs to be explained and followed up because the balance between the proinflammatory system and the anti-inflammatory system tends towards proinflammation, when compared to non-pregnant women.8, 9

There are studies showing that hyperglycaemia initiates inflammation and causes the secretion of cytokines, which are protein molecules that function as immune mediators and regulators expressed by various cell types, and the formation of the acute phase response.9, 10 In addition to the physiological role in the fetoplacenta during pregnancy, the expression of cytokines at abnormal levels has a role in the pathophysiology of GDM.10, 11

In recent years, there have been increasing studies on the role of the inflammatory system in the pathogenesis of T2DM and GDM.12, 13 Because of the similarity between T2DM and GDM and the clear relationship between type II diabetes and inflammation, it has been hypothesised that inflammation may also be involved in the pathophysiology of GDM.14, 15 During pregnancy, the increase in cytokines such as interferon-gamma (IFN-G) and tumour necrosis factor-alpha (TNF-A) synthesised by Th1, the producer of proinflammatory cytokines, jeopardises the pregnancy, while IL-4, which is synthesised by Th2, is one of the anti-inflammatory cytokines. Increased synthesis of IL-6 and IL-10 ensures the continuation of a normal pregnancy period. IL-10 production is related to genetic variations in its promoter region, and this region controls transcription and contains SNPs that are related to diabetes and its complications.16, 17 In addition, inflammation caused by secreted cytokines is thought to be associated with increased insulin resistance in pregnant women with gestational diabetes.18

Th1 cells initiate inflammation by acting on the cell-mediated immune system and are therefore considered cytotoxic agents. However, Th2 cells are effective in humoral immunity and regulate the inflammatory response.19 Th1/Th2 changes have been observed not only in normal pregnancies, but also in pregnancies complicated by diabetes. According to the results of clinical and experimental studies, it has been suggested that while the Th1 response decreases during pregnancy, the Th2 response increases.20 Studies have shown that Th2 response predominates with a successful pregnancy, while Th1 activity is prominent in spontaneous abortions and pre-eclampsia. However, since it is associated with Th2 immunity in recurrent miscarriages, the Th1/Th2 balance was insufficient to explain the mechanism preventing foetal allograft rejection.21, 22

Placenta-specific gene 8 (PLAC8) is one of the highly conserved placental regulatory genes among placental mammals. It promotes invasion and migration of human trophoblast cells during implantation. It is highly expressed in serumcytoid dendritic cells and tissues of the immune system such as bone marrow, lymph nodes, and spleen in adult mammals.23