Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

Yu, Seong‐Lan; Kim, Tae Hyun; Han, Young Ho; Kang, Yujin; Jeong, Daun; Lee, Dong Chul; Kang, Jaeku; Park, Seok‐Rae

doi:10.3892/etm.2021.10092

Cited by 13 publications

(13 citation statements)

References 74 publications

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“…Previously, we performed next-generation sequencing to identify RNAs and non-coding RNAs related to embryo-implantation receptivity and found that miR-182-5p was more highly expressed in the proliferative phase than in the secretory phase during the endometrial receptivity period [ 16 ]. To validate the differential expression of miR-182-5p, we quantified miR-182-5p in the proliferative and secretory phases of normal endometrium tissues and during the secretory phase of infertility ( Figure 1 A).…”

Section: Resultsmentioning

confidence: 99%

“…In some cancers, miR-182 promotes tumor metastasis by upregulating epithelial–mesenchymal transition (EMT)-related genes [ 10 , 11 , 12 , 13 , 14 , 15 ]. We previously reported that miR-182 was downregulated in the mid-secretory phase, between 20 and 24 days of the menstrual cycle, during the window of implantation (WOI) in the endometrium [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

“…NDRG1 was expressed at higher levels in the secretory phase of the endometrium than in the proliferative phase [ 16 , 17 ]. Altmäe et al (2017) suggested that NDRG1 acts as a transcriptomic biomarker for endometrial receptivity [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

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The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway

Kang

Jeong

et al. 2022

IJMS

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Endometrial receptivity is essential for successful pregnancy, and its impairment is a major cause of embryo-implantation failure. MicroRNAs (miRNAs) that regulate epigenetic modifications have been associated with endometrial receptivity. However, the molecular mechanisms whereby miRNAs regulate endometrial receptivity remain unclear. Therefore, we investigated whether miR-182 and its potential targets influence trophoblast cell attachment. miR-182 was expressed at lower levels in the secretory phase than in the proliferative phase of endometrium tissues from fertile donors. However, miR-182 expression was upregulated during the secretory phase in infertile women. Transfecting a synthetic miR-182-5p mimic decreased spheroid attachment of human JAr choriocarcinoma cells and E-cadherin expression (which is important for endometrial receptivity). miR-182-5p also downregulated N-Myc downstream regulated 1 (NDRG1), which was studied further. NDRG1 was upregulated in the secretory phase of the endometrium tissues and induced E-cadherin expression through the nuclear factor-κB (NF-κB)/zinc finger E-box binding homeobox 1 (ZEB1) signaling pathway. NDRG1-overexpressing or -depleted cells showed altered attachment rates of JAr spheroids. Collectively, our findings indicate that miR-182-5p-mediated NDRG1 downregulation impaired embryo implantation by upregulating the NF-κB/ZEB1/E-cadherin pathway. Hence, miR-182-5p is a potential biomarker for negative selection in endometrial receptivity and a therapeutic target for successful embryo implantation.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway

Kang

Jeong

et al. 2022

IJMS

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“…The human endometrium is a highly self-renewing tissue that is periodically shed, repaired, regenerated and remodeled, under the coordination of estrogen and progesterone, in preparation for embryo implantation [ 18 ]. Recently published studies analyzed the gene expression profiles between proliferative and mid-secretory endometria in fertile women, DEGs upregulated in the proliferative endometrium were significantly enriched in cell cycle, whereas downregulated DEGs were significantly enriched in immune system process and immune response [ 19 ]. The proliferative phase, which occurs following menstruation and precedes ovulation, is marked by the active growth of several cell types including HESCs, epithelial, and endothelial cells [ 20 ], and by ovulation, the average thickness of the endometrium reached about 12 mm, while during the luteal phase, endometrial growth tends to plateau and turned to differentiation [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium

Yao

Dong

et al. 2022

Reprod Biol Endocrinol

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Background Thin endometrium (TE) is a challenging clinical issue in the reproductive medicine characterized by inadequate endometrial thickness, poor response to estrogen and no effective treatments currently. At present, the precise pathogenesis of thin endometria remains to be elucidated. We aimed to explore the related molecular mechanism of TE by comparing the transcriptome profiles of late-proliferative phase endometria between TE and matched controls. Methods We performed a bulk RNA-Seq (RNA-sequencing) of endometrial tissues in the late-proliferative phase in 7 TE and 7 matched controls for the first time. Differential gene expression analysis, gene ontology enrichment analysis and protein-protein interactions (PPIs) network analysis were performed. Immunohistochemistry was used for molecular expression and localization in endometria. Human endometrial stromal cells (HESCs) were isolated and cultured for verifying the functions of hub gene. Results Integrative data mining of our RNA-seq data in endometria revealed that most genes related to cell division and cell cycle were significantly inhibited, while inflammation activation, immune response and reactive oxygen species associated genes were upregulated in TE. PBK was identified as a hub of PPIs network, and its expression level was decreased by 2.43-fold in endometria of TE patients, particularly reduced in the stromal cells, which was paralleled by the decreased expression of Ki67. In vitro experiments showed that the depletion of PBK reduced the proliferation of HESCs by 50% and increased the apoptosis of HESCs by 1 time, meanwhile PBK expression was inhibited by oxidative stress (reduced by 76.2%), hypoxia (reduced by 51.9%) and inflammatory factors (reduced by approximately 50%). These results suggested that the insufficient expression of PBK was involved in the poor endometrial thickness in TE. Conclusions The endometrial transcriptome in late-proliferative phase showed suppressed cell proliferation in women with thin endometria and decreased expression of PBK in human endometrial stromal cells (HESCs), to which inflammation and reactive oxygen species contributed.

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“…High levels of progesterone in the post-ovulatory phase modulate the endometrial gene expression required for implantation by regulating DNA methylation [75][76][77], and alterations in the DNA methylation of 448 sites have been associated with defective endometrial receptivity and consequently in recurrent pregnancy failure [75,78]. Moreover, different non-coding transcripts like lncRNAs and miRNAs are involved in endometrial receptivity regulation [79].…”

Section: Pre-receptive and Receptive Endometriummentioning

confidence: 99%

Epigenetics of pregnancy: looking beyond the DNA code

Zuccarello

Sorrentino

Brasson

et al. 2022

J Assist Reprod Genet

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Epigenetics is the branch of genetics that studies the different mechanisms that influence gene expression without direct modification of the DNA sequence. An ever-increasing amount of evidence suggests that such regulatory processes may play a pivotal role both in the initiation of pregnancy and in the later processes of embryonic and fetal development, thus determining long-term effects even in adult life. In this narrative review, we summarize the current knowledge on the role of epigenetics in pregnancy, from its most studied and well-known mechanisms to the new frontiers of epigenetic regulation, such as the role of ncRNAs and the effects of the gestational environment on fetal brain development. Epigenetic mechanisms in pregnancy are a dynamic phenomenon that responds both to maternal–fetal and environmental factors, which can influence and modify the embryo-fetal development during the various gestational phases. Therefore, we also recapitulate the effects of the most notable environmental factors that can affect pregnancy and prenatal development, such as maternal nutrition, stress hormones, microbiome, and teratogens, focusing on their ability to cause epigenetic modifications in the gestational environment and ultimately in the fetus. Despite the promising advancements in the knowledge of epigenetics in pregnancy, more experience and data on this topic are still needed. A better understanding of epigenetic regulation in pregnancy could in fact prove valuable towards a better management of both physiological pregnancies and assisted reproduction treatments, other than allowing to better comprehend the origin of multifactorial pathological conditions such as neurodevelopmental disorders.

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Transcriptomic analysis and competing endogenous RNA network in the human endometrium between proliferative and mid‑secretory phases

Cited by 13 publications

References 74 publications

The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway

The miR-182-5p/NDRG1 Axis Controls Endometrial Receptivity through the NF-κB/ZEB1/E-Cadherin Pathway

Down-regulation of PBK inhibits proliferation of human endometrial stromal cells in thin endometrium

Epigenetics of pregnancy: looking beyond the DNA code

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