CD97 Is Decreased in Preeclamptic Placentas and Promotes Human Trophoblast Invasion Through PI3K/Akt/mTOR Signaling Pathway

Shen, Huaxiang; Jin, Mingzhu; Gu, Shengyi; Wu, Yong; Yang, Mengnan; Hua, Xiaolin

doi:10.1007/s43032-020-00183-w

Cited by 11 publications

(4 citation statements)

References 27 publications

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“…In the literature, this issue has been studied very limitedly. Similar to the study of Shen et al [ 37 ], we showed that CD97 immunohistochemical staining of placental sections was less in the PE group. In our study, maternal blood serum levels of CD97 elisa were consistent with CD97 immunohistochemical staining of placental sections.…”

Section: Discussionsupporting

confidence: 90%

CD97 expression level and its effect on cell adhesion in Preeclampsia

Atıgan

Tan

Çetin

et al. 2022

BMC Pregnancy Childbirth

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Objectives Cellular interactions and cell adhesion underlie preeclampsia (PE). The aim of the current study is to investigate the role of cell adhesion molecules such as CD97, neural (N)-cadherin, epithelial (E) -cadherin and integrin beta-4 in PE. Methods This prospective study included 20 pregnant women with PE and a control group of 16 healthy pregnant women who were matched for age, gestational age, gravida and parity. Standard blood tests and placental cell adhesion molecule immunohistochemical staining were examined. Results The creatinine, uric acid and lactate dehydrogenase (LDH) levels from standard blood tests were found to be statistically higher in the PE group (p = 0.002, p = 0.000, p = 0.001; respectively). In the PE group, the CD97 maternal serum level was statistically significantly lower, as was its immunohistochemical expression in placental sections (p = 0.028, p = 0.000; respectively). The E-cadherin expression score was statistically higher in the PE group compared to the control group (3,65 ± 1,84 vs 2,06 ± 1,76 respectively; p = 0.003). The N-cadherin expression score was statistically lower in the PE group compared to the control group (1,50 ± 0,82 vs 2,43 ± 1,59 respectively; p = 0.049). Integrin beta-4 was not statistically different between groups. Conclusions Cellular interaction may be responsible for PE as in cancer. A balance in intercellular communication, as researched in cancer therapy, may offer the solution in PE.

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Section: Discussionsupporting

confidence: 90%

CD97 expression level and its effect on cell adhesion in Preeclampsia

Atıgan

Tan

Çetin

et al. 2022

BMC Pregnancy Childbirth

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“…Genes upregulated in EVT after exposure to uNK cytokines are involved in several different biological processes (Figure S5D). In line with the morphological and cellular changes supporting enhancement of EVT differentiation, genes involved in EMT (MCAM, TGFBR2, HEG1, VGLL3) [37][38][39][40] , cell invasion (ADGRE5, MMP11, TIMP3, S100P) [41][42][43] , and fusion (CD9, ADAM12) [44][45][46] are up-regulated by uNK cytokines (Figures 4A and S5D).…”

Section: Unk-derived Cytokines Affect Evt Behaviour By Regulating Div...mentioning

confidence: 81%

Successful placentation in human pregnancy is regulated by reciprocal interactions between maternal uterine NK cells and fetal placental trophoblast

Li¹,

Sharkey²,

Sheridan³

et al. 2023

Preprint

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Fetal growth and development during human pregnancy depends on delivery of adequate maternal oxygen and nutrients to the fetus via the placenta. In humans, the balanced invasion of fetal placental trophoblast cells into the maternal uterine lining, where they interact with uterine natural killer cells (uNK), is thought to be critical for a successful pregnancy but exactly how this influences reproductive outcomes remains undefined. Here, we used our trophoblast organoid model and primary tissue samples to determine how uNK affect placentation. By locating potential interaction axes between primary trophoblast cells and uNK using single cell transcriptomics, and in vitro modelling of these interactions in trophoblast organoids, we identify a uNK-derived cytokine signal that promotes trophoblast differentiation by enhancing epithelial-mesenchymal transition and increasing trophoblast cells at the late stage of the invasive pathway. Moreover, it affects transcriptional programs involved in increasing blood flow, placental access to nutrients, and dampening inflammatory and adaptive immune responses, as well as gene signatures associated with disorders of pregnancy such as pre-eclampsia. Our findings shed new light on how optimal immunological interactions between maternal uNK cells and fetal trophoblast enhance reproductive success.

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“…The mRNA level of ITGB2 was decreased significantly in women with recurrent implantation failure ( 91 ), which revealed the effect of ITGB2 in embryo implantation. ADGRE5 promoted trophoblast invasion via the PI3K/Akt/mTOR signaling pathway, which was decreased in preeclampsia patients ( 92 ). We came to the conclusions diametrically different from others; however, our result did reflect interaction strength but not the expression levels of genes.…”

Section: Discussionmentioning

confidence: 99%

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

Xie

et al. 2023

Front. Endocrinol.

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ObjectiveAutoimmune thyroid disease (AITD) is known to be associated with unexplained infertility in women. Although the presence of antithyroid antibodies have been speculated to be a marker of an immune imbalance that might lead to implantation failure, its underlying mechanism influencing the endometrial receptivity remains to be elucidated. In this study, we used single-cell RNA sequencing (scRNA-seq) to dissect immune microenvironment in endometrium of AITD patients during window of implantation (WOI).MethodsWe collected CD45+ immune cell populations of endometrium samples of unexplained infertile women with AITD (n=3), as well as samples of AITD- controls (n=3). The cells were then processed with 10X Genomics Chromium for further analysis.ResultsWe characterized 28 distinct immune cell subtypes totally, and uncovered differences in the composition and gene expression patterns between AITD patients and controls. The proportions of T CD4+, cNK, ILC3, T CD8+GZMK+, T CD8+ Cytotoxic and ILC3 CD3E- cells were increased, and CD366+ uNK1 was decreased in AITD+ patients. And the abnormal expression of GNLY and chemokines was observed in AITD patients. In addition, uNK and T CD8+ Cytotoxic cells showed lower cytotoxicity but activation of immune response. Genes enriched in cell adhesion of ILC3 and Tregs were downregulated, while the number of ILC3 and Tregs were increased.ConclusionImmune imbalance exists in endometrium during WOI, which may impact embryo implantation.

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CD97 Is Decreased in Preeclamptic Placentas and Promotes Human Trophoblast Invasion Through PI3K/Akt/mTOR Signaling Pathway

Cited by 11 publications

References 27 publications

CD97 expression level and its effect on cell adhesion in Preeclampsia

CD97 expression level and its effect on cell adhesion in Preeclampsia

Successful placentation in human pregnancy is regulated by reciprocal interactions between maternal uterine NK cells and fetal placental trophoblast

Autoimmune thyroid disease disrupts immune homeostasis in the endometrium of unexplained infertility women—a single-cell RNA transcriptome study during the implantation window

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