Activating transcription factor 3 promotes embryo attachment via up-regulation of leukemia inhibitory factor in vitro

Cheng, Xi; Liu, Jingyu; Shan, Huizhi; Sun, Lihua; Huang, Chenyang; Yan, Qiang; Jiang, Ruiwei; Zhou, Jianjun; Yan, Guijun; Sun, Haixiang

doi:10.1186/s12958-017-0260-7

Cited by 17 publications

(17 citation statements)

References 35 publications

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Section: Introductionmentioning

confidence: 99%

“…Several associated transcription factors reportedly participate in the preparation of human endometrial receptivity, such as homeobox containing transcription factor 10 (Hoxa10) 21 , signal transducer and activator of transcription 3 (STAT3) 22 , and activating transcription factor 3 (ATF3) 23 . Furthermore, LIF is considered to be a direct downstream target gene of ATF3 23 . We have previously demonstrated that Krüppel-like factor 12 (KLF12) is expressed in the glandular epithelium (GE) and stromal cells of secretory-phase endometrial tissue and that KLF12 negatively regulates endometrial decidualization through the transcriptional repression of target genes both in vitro and in vivo 24 .…”

Section: Introductionmentioning

confidence: 99%

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Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure

et al. 2018

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Recurrent implantation failure (RIF) caused by various etiological factors remains a challenge for fertility clinicians using assisted reproductive technology (ART) worldwide. Dysregulation of leukemia inhibitory factor (LIF) in the endometria of women with RIF is involved in impaired endometrial receptivity and embryo adhesion. However, the mechanism through which LIF expression is regulated in women with RIF is still poorly understood. Our previous study noted that the abnormally increased endometrial Krüppel-like factor 12 (KLF12) in RIF women led to impaired decidualization and embryo implantation. Here, we further found that KLF12 inhibited embryo adhesion in vivo and in vitro by repressing LIF expression. Mechanistically, KLF12 bound to conserved sites (CAGTGGG, −6771 to −6765 and −7115 to −7109) within the LIF promoter region and repressed LIF transcription directly. Exogenous LIF significantly reversed the KLF12-mediated repression of BeWo spheroid adhesion. KLF12 expression was reduced significantly in Ishikawa cells treated with progestogen, which was due to the activation of Akt signaling. These findings may provide novel potential therapeutic regimens for patients with RIF and disrupted endometrial receptivity.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure

et al. 2018

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“…In our previous study, we found that ATF3 was located in both human endometrial epithelial cells and stromal cells, and its expression was dysregulated in RIF patients. In epithelial cells, ATF3 could promote embryo adhesion in vitro by transcriptionally increasing LIF expression 32 . In this study, we focused on the stromal cells to investigate the function of ATF3 on decidualization.…”

Section: Discussionmentioning

confidence: 99%

ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients

Wang

Liu

et al. 2021

Cell Death Dis

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Decidualization is a complex process involving cellular proliferation and differentiation of the endometrial stroma and is required to establish and support pregnancy. Dysregulated decidualization has been reported to be a critical cause of recurrent implantation failure (RIF). In this study, we found that Activating transcription factor 3 (ATF3) expression was significantly downregulated in the endometrium of RIF patients. Knockdown of ATF3 in human endometrium stromal cells (hESCs) hampers decidualization, while overexpression could trigger the expression of decidual marker genes, and ameliorate the decidualization of hESCs from RIF patients. Mechanistically, ATF3 promotes decidualization by upregulating FOXO1 via suppressing miR-135b expression. In addition, the endometrium of RIF patients was hyperproliferative, while overexpression of ATF3 inhibited the proliferation of hESCs through CDKN1A. These data demonstrate the critical roles of endometrial ATF3 in regulating decidualization and proliferation, and dysregulation of ATF3 in the endometrium may be a novel cause of RIF and therefore represent a potential therapeutic target for RIF.

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“…ATF3 is induced by a variety of signals, including cell cycling, neutrophil migration and sexual differentiation [27][28][29]. Cheng et al revealed that ATF3 has an important role in regulating human endometrial receptivity and embryo attachment in vitro via up-regulation of leukemia inhibitory factor [30]. Those 461 genes were enriched in the biological processes of anion transmembrane transport, response to corticosteroid and response to glucocorticoid (P-value < 0.05).…”

Section: Functionally Important Regulatory Modules Are Identi Ed In Ementioning

confidence: 99%

Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation Dynamics During Early Embryonic Development

Chen¹,

Li²,

Chen³

et al. 2021

Preprint

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BackgroundSingle-cell RNA-seq (scRNA-seq) technologies greatly revolutionized our understanding of cell-to-cell variability of gene expression. Although several studies investigated the expression profile of early embryos, they mainly focused on the expression changes at gene level. Here we systematically explored the gene expression dynamics of human early embryonic development from expression level, alternative splicing, isoform switching and expression regulatory network. ResultsWe found that the genes involved in significant changes of these three aspects are all gradually decreased along embryonic development from E3 to E7 stage. Moreover, these three types of variations are complementary for profiling expression dynamics and they vary greatly across embryonic development as well as between different sexes. Strikingly, only a small number of genes exhibited prominent expression level changes between male and female embryos in E3 stage, whereas many more genes showed variations in alternative splicing and major isoform switching. Additionally, we identified functionally important specific gene regulatory modules for each stage and revealed dynamic usage of transcription factor binding motifs (TFBMs). ConclusionsCollectively, our study gain insights into the expression dynamics of early embryonic development from expression level, alternative splicing, isoform switching and gene regulatory networks, which could benefit the understanding of underlying mechanism of embryonic development.

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Activating transcription factor 3 promotes embryo attachment via up-regulation of leukemia inhibitory factor in vitro

Cited by 17 publications

References 35 publications

Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure

Increased Krüppel-like factor 12 impairs embryo attachment via downregulation of leukemia inhibitory factor in women with recurrent implantation failure

ATF3 deficiency impairs the proliferative–secretory phase transition and decidualization in RIF patients

Single-Cell Analysis of Alternative Splicing and Gene Regulatory Network Reveals Remarkable Expression and Regulation Dynamics During Early Embryonic Development

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