The Maternal–Fetal Interface in Small-for-Gestational-Age Pregnancies Is Associated With a Reduced Quantity of Human Decidual NK Cells With Weaker Functional Ability

Lin, Fang‐Yue; Yang, Chuan; Feng, Ting; Yang, Sun; Zhou, Rong

doi:10.3389/fcell.2020.00633

Cited by 10 publications

(8 citation statements)

References 58 publications

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“…There are three sub-types of transforming growth factor (TGF) family, namely α, β, and γ, whose expression can be detected at the maternal-fetal interface, indicating their importance in the process of implantation [7][8][9]. TGF family exists in endometrium and plays an important role in regulating cell proliferation, decidualization, and implantation [10,11].…”

Section: Discussionmentioning

confidence: 99%

Up-regulation of TGFBI and TGFB2 in the plasma of gestational diabetes mellitus patients and its clinical significance

et al. 2021

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Background Gestational diabetes mellitus (GDM) reflects a deficiency in the relative need for insulin during pregnancy, as well as temporary metabolic stress in the placenta and fetus. Our study aimed to research the potential diagnostic value of transforming growth factor-beta-induced protein ig-h3 (TGFBI) and transforming growth factor beta-2 proprotein (TGFB2) for GDM patients. Methods Online database Gene Expression Omnibus (GEO) was used to screen for different expressed genes (DEGs) associated with GDM. Meanwhile, KEGG and GO were used to analyze the molecular functions as well as pathways of enriched DEGs. One hundred ten pregnant women diagnosed with GDM and 110 healthy controls were enrolled, of whose placenta and fasting venous blood samples were collected. mRNA expression levels were determined by real-time quantitative polymerase chain reaction (RT-qPCR), and fasting blood glucose (FBG) was measured by the clinical lab of hospital. Furthermore, receiver operating characteristics curve (ROC) analysis was performed to evaluate the sensitivity and specificity of detection indexed in the placenta and plasma of GDM patients. Finally, Pearson and Spearman analysis was used for the correlation analysis. Results After GEO data analysis, TGFBI and TGFB2 were identified as the most significantly up-regulated genes of GDM. TGFBI and TGFB2 expressions in placenta and plasma samples of GDM patients were in line with bioinformatic analysis. Meanwhile, the area under the curve (AUC) of TGFBI in the placenta and plasma for the diagnosis of GDM were 0.8783 (95% CI, 0.8281 to 0.9284) and 0.7832 (95% CI, 0.7215 to 0.8449) while for TGFB2 were 0.9225 (95% CI, 0.8829 to 0.9621) and 0.8961 (95% CI, 0.8526 to 0.9396). Besides, levels of TGFBI along with TGFB2 in the placenta were positively correlated with that in the plasma of GDM patients. Furthermore, both TGFBI and TGFB2 expressions in the plasma were positively correlated with FBG levels of the GDM patients. Conclusions TGFBI and TGFB2 were up-regulated in the placenta and plasma of GDM patients, and TGFBI and TGFB2 in the plasma are potent to be diagnostic markers for the GDM. Keywords Biomarker • Different expressed genes (DEGs) • Gestational diabetes mellitus (GDM) • GEO database • Transforming growth factor beta-2 proprotein (TGFB2) • Transforming growth factor-beta-induced protein ig-h3 (TGFBI)

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Section: Discussionmentioning

confidence: 99%

Up-regulation of TGFBI and TGFB2 in the plasma of gestational diabetes mellitus patients and its clinical significance

et al. 2021

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“…In PE pregnancies, dNK cells exhibit a reduced promotion effect on first trimester trophoblast invasion and migration when compared to normal controls. In small-for-gestational-age (SGA) pregnancies, dNK cells show impairments in proliferation, migration, invasion, and tube formation of trophoblast cells or vascular endothelial cells compared to those in appropriate-for-gestational-age (AGA) pregnancies [ 35 ].…”

Section: Dnk Cells In Pregnancymentioning

confidence: 99%

miRNAs in decidual NK cells: regulators worthy of attention during pregnancy

Feng

Zhou

et al. 2021

Reprod Biol Endocrinol

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The critical immune effectors, including T, B, and natural killer (NK) cells, dendritic cells, and macrophages participate in regulating immune responses during pregnancy. Among these immune cells, decidual NK (dNK) cells are involved in key placental development processes at the maternal–fetal interface, such as uterine spiral artery remodeling, trophoblast invasion, and decidualization. Mechanistically, dNK cells significantly influence pregnancy outcome by secreting cytokines, chemokines, and angiogenic mediators and by their interactions with trophoblasts and other decidual cells. MicroRNAs (miRNAs) are small non-coding RNA molecules that participate in the initiation and progression of human diseases. Although the functions of circulating miRNAs in pathological mechanism has been extensively studied, the regulatory roles of miRNAs in NK cells, especially in dNK cells, have been rarely reported. In this review, we analyze the effects of miRNA regulations of dNK cell functions on the immune system during gestation. We discuss aberrant expressions of certain miRNAs in dNK cells that may lead to pathological consequences, such as recurrent pregnancy loss (RPL). Interestingly, miRNA expression patterns are also different between dNK cells and peripheral NK (pNK) cells, and pNK cells in the first- and third‐trimester of gestation. The dysregulation of miRNA plays a pivotal regulatory role in driving immune functions of dNK and pNK cells. Further understanding of the molecular mechanisms of miRNAs in dNK cells may provide new insights into the development of therapeutics to prevent pregnancy failure.

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“…In aged mouse and humans, the resolution of endometriosis is delayed [34]. Chronic inflammation in endometrial tissue decreases the telomerase activity of several cells, impeding their optimal physiological response in mouse [34] and humans [21,[35][36][37][38][39]. trNK cells could also be affected by the low telomerase response [34].…”

Section: Nk Cells and Endometrial Diseasementioning

confidence: 99%

“…trNK cells could also be affected by the low telomerase response [34]. On the other hand, senescent cells may activate the cytotoxic response of cNK cells [34][35][36][37][38][39] against autologous cells and, in consequence, generate more cell death maintaining the local chronic inflammatory response.…”

Section: Nk Cells and Endometrial Diseasementioning

confidence: 99%

“…In humans, NK cells, macrophages, and T cells are responsible for maintaining the local inflammatory response [35][36][37][38][39][40]. The role of TH17 and IFN γ has been widely discussed; however, the control of inflammation in the tissue is not achieved in many patients despite surgery or other therapeutic options raising the question of a wider variety of endometrial diseases [21,[36][37][38][39]. One of the often-overlooked events is autoantibodies, which can play an essential role in maintaining the inflammatory response [40][41][42].…”

Section: Nk Cells and Endometrial Diseasementioning

confidence: 99%

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A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

Garmendia

Sanctis

2021

Immuno

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NK cells are lymphocytes involved in the innate and adaptative immune response. These cells are located in peripheral blood and tissues with ample functions, from immune vigilant to tolerogenic reactions. In the endometrium, NK cell populations vary depending on age, hormones, and inflammation. When pregnancy occurs, tissue-resident NK cells and conventional NK cells are recruited to protect the fetus, a tolerogenic response. On the contrary, in the inflamed endometrium, various inflammatory cells down-regulate NK tolerance and impair embryo implantation. Therefore, NK cells’ pharmacological modulation is difficult to achieve. Several strategies have been used, from progesterone, lipid emulsions to steroids; the success has not been as expected. However, new therapeutic approaches have been proposed to decrease the endometrial inflammatory burden and increase pregnancy success based on understanding NK cell physiology.

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The Maternal–Fetal Interface in Small-for-Gestational-Age Pregnancies Is Associated With a Reduced Quantity of Human Decidual NK Cells With Weaker Functional Ability

Cited by 10 publications

References 58 publications

Up-regulation of TGFBI and TGFB2 in the plasma of gestational diabetes mellitus patients and its clinical significance

Up-regulation of TGFBI and TGFB2 in the plasma of gestational diabetes mellitus patients and its clinical significance

miRNAs in decidual NK cells: regulators worthy of attention during pregnancy

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

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