TGFβ superfamily signaling and uterine decidualization

Ni, Nan; Li, Qinglei

doi:10.1186/s12958-017-0303-0

Cited by 68 publications

(59 citation statements)

References 112 publications

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“…TGFB1 , expressed in decidua and placenta in total RNA-seq, is a key upstream regulator in all cell types, confirming TGFβ1 is a significant coordinator of placental development at the maternal-fetal interface [34]. TGFB1 is specifically expressed in the EVT subcluster in trophoblasts which may coordinate invasion of EVTs with differentiation of STBs through its receptor TGFBR1 , which is expressed in both EVT and STB subclusters in our study (data not shown) and by others [27].…”

Section: Discussionmentioning

confidence: 99%

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing

Sun

Gonzalez

Deng

et al. 2019

Preprint

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2 2 3 1 identified five major cell types (trophoblasts, stromal cells, hofbauer cells, antigen 3 2 presenting cells and endothelial cells) with unique crosstalk at the maternal-fetal 3 3 interface. We identified seven unique trophoblast subclusters, including new subtypes 3 4 that transition into the terminal cell types, extra-villous trophoblasts and 3 5syncytiotrophoblasts. As fetal sex impacts pregnancy, we analyzed sex differences in 3 6 each cell type and identified differences in immune cell function. TGFβ1, β -estradiol, 3 7 and dihydrotestosterone emerge as upstream regulators of sexually dimorphic genes in 3 8 a cell type specific manner. Thus, the fetal contribution at the maternal-fetal interface is 3 9 cell and sex specific.4 0 Key words 4 1 Maternal-fetal interface, first trimester, ongoing pregnancy, human early pregnancy, 4 2 placenta, single cell RNA sequencing, sexual dimorphism, placenta cell types, receptor, 4 3 ligand 4 4 placental development that might impact maternal-fetal communication and contribute 6 9 to overall outcomes. 7 0 Results 7 1 7 2 RNA-sequencing of matched decidua and placenta tissue from first trimester 7 3 To identify normal early gene expression at the maternal-fetal interface, total RNA-7 4 sequencing for matched decidua (maternal) and chorionic villi (fetal placenta) was 7 5 performed. Principal component 1 shows that tissue type explains most of the difference 7 6 between samples. Principal component 2 corresponds to fetal sex (Figure S1). 7 7 RNA-sequencing identified 16,035 genes reaching threshold FPKM>1 and Z-score>0 in 7 8 decidua, placenta or both. Of these, 12,479 (77.8%) are protein-coding genes, including 7 9 3002 significantly differentially expressed genes (DEGs) with FDR<0.10 (Figure S2A, 8 0 Table S1). Over a quarter of protein-coding DEGs are tissue-unique at the maternal-8 1 fetal interface, meaning they are expressed in either decidua or placenta, but not both. 8 2 There are 2223 protein-coding DEGs upregulated in decidua compared to placenta 8 3 ("decidua-upregulated"), including 827 only expressed in decidua ("decidua-unique"). 8 4 There are 779 protein-coding DEGs upregulated in placenta compared to decidua 8 5 ("placenta-upregulated"), including 60 only expressed in placenta tissue ("placenta-8 6 unique").8 7 Receptors and ligands differentially expressed at the maternal-fetal interface 8 8To investigate maternal-fetal communication, we focused on receptor and ligand DEGs. 8 9We identified 818 receptors expressed at the maternal-fetal interface (TableS2) [7][8][9] 9 0 with 356 receptors significantly differentially expressed (FDR<0.10) between decidua 9 1 5 and placenta, including 290 decidua-upregulated receptors and 66 placenta-9 2 upregulated receptors (Figure S2B). Half of decidua-upregulated receptors are also 9 3 decidua-unique (146/290; 50.3%). The 5 decidua-unique receptors with highest fold-9 4 change over placenta are PIGR (FC = 215.3), GABRP (FC = 165.4), CDHR1 (FC = 9 5 156.5), TSPAN1 (FC = 149.1), and SCARA5 (FC = 125.4) (Table S2). Of t...

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Section: Discussionmentioning

confidence: 99%

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing

Sun

Gonzalez

Deng

et al. 2019

Preprint

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“…Decidualization is a complex biological process, in which the endometrium undergoes extensive remodeling. ESCs undergo morphological, functional, and genetic changes to support embryo implantation and development . Previous studies have confirmed that CXCL16 is highly expressed in decidual tissue.…”

Section: The Role Of Cxcl16 In Normal Pregnancymentioning

confidence: 96%

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies

Shi

Yang

Fan

et al. 2020

American J Rep Immunol

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The survival and development of a semi‐allogeneic fetus during pregnancy require the involvement of a series of cytokines and immune cells. Chemokines are a type of special cytokine those were originally described as having a role in leukocyte trafficking. CXC chemokine ligand (CXCL) 16 is a member of the chemokine family, and CXC chemokine receptor (CXCR) 6 is its sole receptor. Emerging evidence has shown that CXCL16/CXCR6 is expressed at the maternal‐fetal interface, by cell types that include trophoblast cells, decidual stroma cells, and decidual immune cells (eg, monocytes, γδT cells, and natural killer T (NKT) cells). The regulation of expression of CXCL16 is quite complex, and this process involves a multitude of factors. CXCL16 exerts a critical role in the establishment of a successful pregnancy through a series of molecular interactions at the maternal‐fetal interface. However, an abnormal expression of CXCL16 is associated with certain pathological states associated with pregnancy, including recurrent miscarriage, pre‐eclampsia, and gestational diabetes mellitus (GDM). In the present review, the expression and pleiotropic roles of CXCL16 under conditions of physiological and pathological pregnancy are systematically discussed.

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“…TGF-β family proteins are also involved in ovulation, maternal-embryo interactions, embryonic development, such as gastrulation and morphogenesis, and uterine decidualization as well as regulation of male reproductive functions, e.g. testis development [14].…”

Section: Tgf -A Large Familymentioning

confidence: 99%

“…Mouse study shows that estradiol plays an important role in TGF-β1 activation in the uterus [23]. However, its role in decidualization in humans remains unclear; several studies have shown that it acts as an inhibitor of decidualization, decreasing PRL, IGFBP-1 and TF expression [14]. However, other findings suggest that TGF-β1 secreted by endometrial epithelial cells reinforces decidualization and is highly expressed in its active form during this process [23].…”

Section: Transforming Growth Factor Betamentioning

confidence: 99%

“…The signal transduction can proceed in a Smad-independent manner [14]. TGF-β may be involved in the transgenic MAPK kinase (mitogen-activated protein kinase) transduction pathway as well as Erk and JNK pathway activation [14]. Moreover, ligands of the TGF-β receptors may interact outside of TβR with endoglin, or beta-linked glycans eg.…”

Section: Tgfb -Signalling Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

Transforming growth factor (TGF) – is it a key protein in mammalian reproductive biology?

Rybska

Knap

Stefańska

et al. 2018

Medical Journal of Cell Biology

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The superfamily of transforming growth factors β (TGF-β) consists of cytokines that are crucial in regulating the organism's biological functions and includes three isoforms of TGF-β protein, Anti-Müllerian Hormone (AMH), inhibin A and B, activins, 20 bone morphogenetic proteins (BMP1-20) and 9 growth factors (GDF1-9). Their signal transduction pathway involves three types of membrane receptors that exhibit a serine/threonine kinase activity, as well as the Smad proteins. After ligand binding, the Smad proteins are phosphorylated and translocated to the nucleus, where they interact with transcription factors and affect gene expression. TGF-β family members are involved in cell growth and differentiation, as well as chemotaxis and apoptosis, and play an important role during an inflammation. Defects in TGF-β proteins or in their signalling pathway underlie many severe diseases, such as systemic lupus, systemic scleroderma, bronchial asthma, atherosclerosis, hyperthyroidism or cancer. These factors are also crucial in mammal reproductive functions, as they are involved in folliculogenesis, steroidogenesis, ovulation, maternal-embryo interaction, embryo development and uterine decidualization. Their defects result in issues with fertility. This review focuses on the relevance of TGF-β family members in a mammal reproduction with an emphasis on three TGF-β isoforms, inhibins A and B, GDF-9 and their signal transduction pathway. Running title: TGFB in mammalian reproduction

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TGFβ superfamily signaling and uterine decidualization

Cited by 68 publications

References 112 publications

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing

The maternal-fetal interface of successful pregnancies and impact of fetal sex using single cell sequencing

The role of CXC chemokine ligand 16 in physiological and pathological pregnancies

Transforming growth factor (TGF) – is it a key protein in mammalian reproductive biology?

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