|
|
Correlation studies of endoplasmic reticulum stress markers in placental dysfunction in gestational diabetes mellitus |
YANG Kun1, LIU Yingchao2, LIU Yanhui1 |
1. Department of Obstetrics, Liaocheng Second People's Hospital/Liaocheng Second Hospital Affiliated to Shandong First Medical University, Liaocheng 252600, China; 2. Department of Clinical Laboratory, Liaocheng Second People's Hospital/Liaocheng Second Hospital Affiliated to Shandong First Medical University, Liaocheng 252600, China |
|
|
Abstract Objective To investigate the role of endoplasmic reticulum stress markers in peripheral blood mononuclear cells (PBMCs) of patients with gestational diabetes mellitus (GDM) in placental dysfunction. Methods Select 100 singleton patients with 30-32 weeks of pregnancy who received outpatient or inpatient treatment at our hospital from January 2022 to June 2023. Among them, 50 outpatient patients were the control group with normal blood glucose regulation during pregnancy.50 hospitalized patients with GDM during mid pregnancy (24-28 weeks of pregnancy) were selected as the study group to achieve blood glucose control through diet or insulin therapy. Expression of endoplasmic reticulum stress (ERs) pathway related biomarkers, including activating transcription factor 4(ATF4) and enhancer binding protein homologous protein (CHOP), analyzed by PCR Results Compared with the control group, fasting blood glucose, blood glucose at 2 hours after 75 g glucose loading, sFlt-1 and sFlt-1/PLGF ratio in GDM group increased significantly, and PLGF level decreased significantly. Compared with the control group, the expression of ATF4 and CHOP genes in monocytes in GDM group increased significantly. For the whole cohort, the expression of ATF4 and CHOP genes in peripheral blood monocytes increased with the increase of sFlt-1/PLGF ratio (F=60.79, 25.58, all P<0.001). Correlation analysis showed that the expression of ATF4 and CHOP genes was positively correlated with the ratio of sFlt-1/PLGF. According to ROC analysis, it was found that the AUC of ATF4 in predicting GDM was 0.801, the sensitivity was 92.1%, and the specificity was 76.0%. The AUC of CHOP for predicting GDM was 0.738, and it had a sensitivity of 75% and a specificity of 80%. Conclusions GDM has adverse effects on placental function. ATF4 and CHOP may be potential markers for early detection of placental endothelial dysfunction in the fetus.
|
Received: 23 January 2024
|
|
|
|
|
[1] 陈阳阳, 周玉博, 杨静, 等. 双胎妊娠孕期体质量对血清高敏C反应蛋白与妊娠期糖尿病关联的影响: 一项队列研究[J]. 北京大学学报 (医学版) , 2022, 54(3) : 427-433. [2] SISSALA N, MYLLYMÄKI E, MOHR F, et al. Hypoxia ameliorates maternal diet-induced insulin resistance during pregnancy while having a detrimental effect on the placenta[J]. Physiol Rep, 2022, 10(9) : e15302. [3] OLMOS-ORTIZ A, FLORES-ESPINOSA P, DÍAZ L, et al. Immunoendocrine dysregulation during gestational diabetes mellitus: The central role of the placenta[J]. Int J Mol Sci, 2021, 22(15) : 8087. [4] LECHNER A C, SLACK J C, CARREON C K, et al.Placental lesions attributed to shallow implantation, excess extravillous trophoblast and decidual hypoxia: Correlation with maternal vascular malperfusion and related obstetric conditions[J]. Placenta, 2023, 139: 61-67. [5] CHEN L, NIE P, YAO L Y, et al.TiO2 NPs induce the reproductive toxicity in mice with gestational diabetes mellitus through the effects on the endoplasmic reticulum stress signaling pathway[J]. Ecotoxicol Environ Saf, 2021, 226: 112814. [6] DOS ANJOS CORDEIRO J M, SANTOS L C, de Oliveira L S, et al. Maternal hypothyroidism causes oxidative stress and endoplasmic reticulum stress in the maternal-fetal interface of rats[J]. Free Radic Biol Med, 2022, 191: 24-39. [7] HEYDARI N, SHARIFI R, NOURBAKHSH M, et al.Long non-coding RNAs TUG1 and MEG3 in patients with type 2 diabetes and their association with endoplasmic reticulum stress markers[J]. J Endocrinol Invest, 2023, 46(7) : 1441-1448. [8] 中华医学会妇产科学分会产科学组, 中华医学会围产医学分会, 中国妇幼保健协会妊娠合并糖尿病专业委员会. 妊娠期高血糖诊治指南 (2022) [第一部分][J]. 中华妇产科杂志, 2022, 57(1) : 3-12. [9] FERNANDES-DA-SILVA A, MIRANDA CS, SANTANA-OLIVEIRA DA, et al. Endoplasmic reticulum stress as the basis of obesity and metabolic diseases: focus on adipose tissue, liver, and pancreas[J]. Eur J Nutr, 2021, 60(6): 2949-2960. [10] SONG F, LEE W D, MARMO T, et al.Osteoblast-intrinsic defect in glucose metabolism impairs bone formation in type II diabetic male mice[J]. Elife, 2023, 12: e85714. [11] NOURBAKHSH M, SHARIFI R, HEYDARI N, et al.Circulating TRB3 and GRP78 levels in type 2 diabetes patients: Crosstalk between glucose homeostasis and endoplasmic reticulum stress[J]. J Endocrinol Invest , 2022, 45(3) : 649-655. [12] MA N, XU N, YIN D, et al.Levels of circulating GRP78 and CHOP in endoplasmic reticulum stress pathways in Chinese type 2 diabetic kidney disease patients[J]. Medicine, 2021, 100(33) : e26879. [13] GIRONA J, RODRÍGUEZ-BORJABAD C, IBARRETXE D, et al. The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario[J]. J Clin Med, 2019, 8(11) : 1793. [14] CHI X, LI Z, ZHANG L, et al.Phoenixin-20 ameliorates gestational diabetes mellitus (GDM) symptoms and placental insults in an experimental mouse model[J]. Int Immunopharmacol, 2021, 101: 108171. [15] DONG Y, RUANO S H, MISHRA A, et al.Adrenomedullin and its receptors are expressed in mouse pancreatic β-cells and suppresses insulin synthesis and secretion[J]. Plos One, 2022, 17(3) : e0265890. [16] ODURO P K, FANG J, NIU L, et al.Pharmacological management of vascular endothelial dysfunction in diabetes: TCM and western medicine compared based on biomarkers and biochemical parameters[J]. Pharmacol Res, 2020, 158: 104893. [17] SHEU W H H, LIN K H, WANG J S, et al. Therapeutic potential of Tpl2 (tumor progression locus 2) inhibition on diabetic vasculopathy through the blockage of the inflammasome complex[J]. Arterioscler Thromb Vasc Biol, 2021, 41(1) : e46-e62. [18] NUZZO A M, GIUFFRIDA D, MORETTI L, et al.Placental and maternal sFlt1/PLGF expression in gestational diabetes mellitus[J]. Sci Rep, 2021, 11(1) : 2312. [19] KARPOVA N S, DMITRENKO O P, BUDYKINA T S.Literature Review: The sFlt1/PLGF Ratio and Pregestational Maternal Comorbidities: New Risk Factors to Predict Pre-Eclampsia[J]. Int J Mol Sci, 2023, 24(7): 6744. [20] GACCIOLI F, SOVIO U, GONG S, et al.Increased placental sFLT1 (soluble fms-like tyrosine kinase receptor-1) drives the antiangiogenic profile of maternal serum preceding preeclampsia but not fetal growth restriction[J]. Hypertension, 2023, 80(2) : 325-334. [21] LI X, YU T, ZHAI M, et al.Maternal cadmium exposure impairs placental angiogenesis in preeclampsia through disturbing thyroid hormone receptor signaling[J]. Ecotoxicol Environ Saf, 2022, 244: 114055. [22] TUGRUL ERSAK D, KARA Ö, YAKUT K, et al.The Association between Placental Abruption and Platelet Indices[J]. Fetal Pediatr Pathol, 2023, 42(3) : 367-375. [23] LIU W, LOU X, ZHANG Z, et al.Association of neutrophil to lymphocyte ratio, platelet to lymphocyte ratio, mean platelet volume with the risk of gestational diabetes mellitus[J]. Gynecol Endocrinol, 2021, 37(2): 105-107. [24] WEI Y, HE A, TANG C, et al.Risk prediction models of gestational diabetes mellitus before 16 gestational weeks[J]. BMC Pregnancy Childbirth, 2022, 22(1) : 889. |
|
|
|