Role of Endogenous Melatonin in the Regulation of Th17/Treg Balance during Pregnancy

Glebezdina, N. S.; Олина, А. А.; Nekrasova, I. V.; Куклина, Е. М.

doi:10.1007/s10517-018-4013-1

Cited by 7 publications

(10 citation statements)

References 14 publications

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“…In the present study, it was observed that the expression of FoxP3 and IL-35 declined in patients with GDM and DPE, suggesting that a reduced production of Treg cells may lead to inflammation. IL-17 and CRP are involved in low-grade inflammation (55). IL-17 is a characteristic inflammatory cytokine expressed by Th17 cells.…”

Section: Discussionmentioning

confidence: 99%

Maternal lipids, BMI and IL‑17/IL‑35 imbalance in concurrent gestational diabetes mellitus and preeclampsia

Cao¹,

Wang

Ting-mei³

et al. 2018

Exp Ther Med

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The objective of the present study was to investigate the role of blood glucose, lipid metabolism, body mass index (BMI), C-reactive protein (CRP) as well as an interleukin (IL)-17/IL-35 imbalance in the pathogenesis of concurrent gestational diabetes mellitus (GDM) and preeclampsia (PE) (DPE). The mRNA expression of forkhead box protein 3 (FoxP3), IL-35 [including Epstein-Barr virus-induced gene 3 (EBI3) and P35 subunits] and IL-17 in the peripheral blood mononuclear cells of patients with DPE (n=30), GDM (n=33), PE (n=33) and normal pregnancy (n=33) were determined by reverse transcription-quantitative polymerase chain reaction. The serum levels of IL-35, IL-17 and CRP were analyzed using ELISA. Serum total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and fasting blood glucose (FBG) were also detected. The levels of low-density lipoprotein (LDL) were calculated using the Friedewald formula. Body weight and height were determined in order to calculate the BMI. It was observed that the levels of FBG were markedly elevated in patients with GDM, PE and DPE. In addition, significantly higher serum TG, TC, LDL and very LDL were detected in patients with GDM, PE and DPE compared with those in subjects with normal pregnancies. By contrast, the concentration of HDL was lower in the patient groups. In addition, higher BMI values were identified in patients with GDM, PE and DPE. A decreased expression of FoxP3, P35 and EBI3 mRNA, and an elevated expression of IL-17 in PBMCs was detected in patients with GDM, PE and DPE. In addition, higher serum levels of IL-17 and CRP, as well as lower levels of IL-35, were observed. Furthermore, in patients with DPE, positive correlations of diastolic blood pressure with IL-17 levels, BMI and TG, as well as IL-17 levels with BMI and proteinuria were identified. In conclusion, the present study indicated that abnormal maternal lipids, hyperglycemia, high BMI, high CRP and IL-17/IL-35 imbalance may have a role in the pathophysiology of DPE. Therefore, pregnant women and clinicians should be made aware that maternal hyperlipidaemia, hyperglycemia, high BMI, high CRP levels and IL-17/IL-35 imbalance may lead to DPE.

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Section: Discussionmentioning

confidence: 99%

Maternal lipids, BMI and IL‑17/IL‑35 imbalance in concurrent gestational diabetes mellitus and preeclampsia

Cao¹,

Wang

Ting-mei³

et al. 2018

Exp Ther Med

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“…Melatonin treatment can reduce lipid peroxidation induced by obstructive cholestasis during the last third of pregnancy in rats by stimulating the expression of components of the endogenous cellular antioxidant defence in the maternal liver 66 . The melatonin levels in hepatocytes are independent of pineal‐derived melatonin, which provides hepatocytes with a buffer against free radicals 29 . Hepatocytes play a role as ‘accessory’ cells in both the afferent and efferent arms of the cell‐mediated immune response 67 .…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin treatment can increase pregnenolone synthesis in the ovary and endometrium, which promotes endometrial development and embryo implantation early in mouse pregnancy 28 . T‐cell subpopulations, IL‐17 (Th17) and regulatory T (Treg) cells, have an essential role during pregnancy, and endogenous melatonin is involved in regulating the Th17/Treg balance during pregnancy in humans 29 . It has been reported that the characteristics of the melatonin secretory rhythm are unaffected by steroids during the oestrous cycle and pregnancy in Ile‐de‐France ewes 30,31 .…”

Section: Introductionmentioning

confidence: 99%

Expression of melatonin receptors and CD4 in the ovine thymus, lymph node, spleen and liver during early pregnancy

et al. 2020

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As a pineal gland hormone, melatonin acts through its receptors to modulate the immune system. The immune system is composed of primary and secondary organs, and immune organs are adapted to the presence of the fetal alloantigen during pregnancy. However, it is unclear whether melatonin affects maternal immune organs during early pregnancy in sheep. In this study, the ovine thymus, lymph node, spleen and liver were sampled at day 16 of the oestrous cycle, and at days 13, 16 and 25 of pregnancy. The expression of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2) and cluster of differentiation 4 (CD4) was detected by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry experiments. Our results showed that during early pregnancy there was an upregulation of MT1 mRNA and protein in the thymus, lymph node and liver, and there was a downregulation in the spleen. The expression of MT2 mRNA and protein was increased in the thymus but decreased in the spleen and liver, and there was no significant change in the lymph node during early pregnancy. CD4 protein was upregulated in the thymus, lymph node and liver, but there were no significant changes in the spleen during early pregnancy. In conclusion, early pregnancy induces tissue-specific expression of MT1, MT2 and CD4, which may be due to the different functions of the thymus, lymph node, spleen and liver. Further, melatonin is involved in immune regulation of the maternal thymus, lymph node, spleen and liver during early pregnancy in sheep.

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“…Both physiological and pharmacological levels of melatonin induce in vitro differentiation of intact CD4 + T cells in Th17 [108]. Recently, ex vivo and in vitro studies using auto-serum as a source of endogenous melatonin, showed differentiation in both CD4 + RORγt + and CD4 + FoxP3 + T cells, leading to an inverse balance of Th17/Treg [109]. Although melatonin's functions on the maternal-fetal immune cells are not completely defined, exogenous melatonin is documented to have beneficial effects for mother and fetus in the context of immunocompromised pregnancy.…”

Section: Melatonin's Action On the Immune Microenvironment At The Matmentioning

confidence: 99%

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

Chuffa

Lupi

Cucielo

et al. 2019

IJMS

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The development of the endometrium is a cyclic event tightly regulated by hormones and growth factors to coordinate the menstrual cycle while promoting a suitable microenvironment for embryo implantation during the “receptivity window”. Many women experience uterine failures that hamper the success of conception, such as endometrium thickness, endometriosis, luteal phase defects, endometrial polyps, adenomyosis, viral infection, and even endometrial cancer; most of these disturbances involve changes in endocrine components or cell damage. The emerging evidence has proven that circadian rhythm deregulation followed by low circulating melatonin is associated with low implantation rates and difficulties to maintain pregnancy. Given that melatonin is a circadian-regulating hormone also involved in the maintenance of uterine homeostasis through regulation of numerous pathways associated with uterine receptivity and gestation, the success of female reproduction may be dependent on the levels and activity of uterine and placental melatonin. Based on the fact that irregular production of maternal and placental melatonin is related to recurrent spontaneous abortion and maternal/fetal disturbances, melatonin replacement may offer an excellent opportunity to restore normal physiological function of the affected tissues. By alleviating oxidative damage in the placenta, melatonin favors nutrient transfer and improves vascular dynamics at the uterine–placental interface. This review focuses on the main in vivo and in vitro functions of melatonin on uterine physiological processes, such as decidualization and implantation, and also on the feto-maternal tissues, and reviews how exogenous melatonin functions from a mechanistic standpoint to preserve the organ health. New insights on the potential signaling pathways whereby melatonin resists preeclampsia and endometriosis are further emphasized in this review.

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Role of Endogenous Melatonin in the Regulation of Th17/Treg Balance during Pregnancy

Cited by 7 publications

References 14 publications

Maternal lipids, BMI and IL‑17/IL‑35 imbalance in concurrent gestational diabetes mellitus and preeclampsia

Maternal lipids, BMI and IL‑17/IL‑35 imbalance in concurrent gestational diabetes mellitus and preeclampsia

Expression of melatonin receptors and CD4 in the ovine thymus, lymph node, spleen and liver during early pregnancy

Melatonin Promotes Uterine and Placental Health: Potential Molecular Mechanisms

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