Genes involved in implantation

2001 ◽  
Vol 13 (1) ◽  
pp. 41 ◽  
Author(s):  
Lois A. Salamonsen ◽  
Guiying Nie ◽  
Eva Dimitriadis ◽  
Lorraine Robb ◽  
Jock K. Findlay
Keyword(s):  
Calcium Binding ◽  
Embryo Implantation ◽  
Hostile Environment ◽  
Mouse Uterus ◽  
Suppressor Factor ◽  
Expression Of Genes ◽  
Molecular Events ◽  
Human Fertility ◽  
Implantation Sites ◽  
Interleukin 11

The endometrium is normally a hostile environment for an embryo, except for a short phase in each reproductive cycle known as the ‘window of receptivity’. The precise molecular events involved in this transformation are not well understood. Application of state-of-the-art techniques of the 1990s has identified some of the genes involved, which are reviewed here. Mice with a null mutation in either the gene for leukemia inhibitory factor or the interleukin-11 receptor α chain are infertile, owing in both cases to a failure of embryo implantation. Both of these genes are expressed in the human endometrium with patterns suggesting a role in human fertility. The technique of RNA differential display has been applied to a comparison of the expression of genes at implantation sites v. inter-implantation sites in the mouse uterus on the first day of implantation, and has defined additional genes whose products may be important for this process. Among these are the calcium-binding protein D9K, the monoclonal non-specific suppressor factor β , and the splicing factor SC35. The major challenge is to determine whether manipulation of such genes can increase or decrease endometrial receptivity in humans.

scholarly journals Cell–Cell Communication at the Embryo Implantation Site of Mouse Uterus Revealed by Single-Cell Analysis

2021 ◽  
Vol 22 (10) ◽  
pp. 5177
Author(s):  
Yi Yang ◽  
Jia-Peng He ◽  
Ji-Long Liu
Keyword(s):  
Single Cell ◽  
Molecular Mechanism ◽  
Single Cell Analysis ◽  
Embryo Implantation ◽  
Cell Communication ◽  
Human Reproduction ◽  
Mouse Uterus ◽  
Implantation Sites ◽  
Low Efficiency ◽  
Signaling Interactions

As a crucial step for human reproduction, embryo implantation is a low-efficiency process. Despite rapid advances in recent years, the molecular mechanism underlying embryo implantation remains poorly understood. Here, we used the mouse as an animal model and generated a single-cell transcriptomic atlas of embryo implantation sites. By analyzing inter-implantation sites of the uterus as control, we were able to identify global gene expression changes associated with embryo implantation in each cell type. Additionally, we predicted signaling interactions between uterine luminal epithelial cells and mural trophectoderm of blastocysts, which represent the key mechanism of embryo implantation. We also predicted signaling interactions between uterine epithelial-stromal crosstalk at implantation sites, which are crucial for post-implantation development. Our data provide a valuable resource for deciphering the molecular mechanism underlying embryo implantation.

scholarly journals Comparative Transcriptomic Analysis of Embryo Implantation in Mice and Rats

2018 ◽  
Vol 50 (2) ◽  
pp. 668-678 ◽  
Author(s):  
Wen-Qian Zhang ◽  
Miao Zhao ◽  
Ming-Yu Huang ◽  
Ji-Long Liu
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Embryo Implantation ◽  
Differentially Expressed ◽  
Rat Uterus ◽  
Mouse Uterus ◽  
Pathway Network ◽  
Implantation Sites ◽  
High Selection ◽  
Transcriptomic Changes

Background/Aims: Embryo implantation is an essential process for eutherian pregnancy, but this process varies across eutherians. The genomic mechanisms that led to the emergence and diversification of embryo implantation are largely unknown. Methods: In this study, we analyzed transcriptomic changes during embryo implantation in mice and rats by using RNA-seq. Bioinformatics and evolutionary analyses were performed to characterize implantation-associated genes in these two species. Results: We identified a total of 518 differentially expressed genes in mouse uterus during implantation, of which 253 genes were up-regulated and 265 genes were down-regulated at the implantation sites compared with the inter-implantation sites. In rat uterus, there were 374 differentially expressed genes, of which 284 genes were up-regulated and 90 genes were down-regulated. A cross-species comparison revealed that 92 up-regulated genes and 20 down-regulated genes were shared. The differences and similarities between mice and rats were investigated further at the gene ontology, pathway, network, and causal transcription factor levels. Additionally, we found that embryo implantation might have evolved through the recruitment of ancient genes into uterine expression. The evolutionary rates of the differentially expressed genes in mouse and rat uterus were significantly lower than those of the non-changed genes, indicating that implantation-related genes are evolutionary conserved due to high selection pressure. Conclusion: Our study provides insights into the molecular mechanisms involved in the evolution of embryo implantation.

scholarly journals Evidence For Hmgn2 Involvement in Mouse Embryo Implantation and Decidualization

2017 ◽  
Vol 44 (5) ◽  
pp. 1681-1695 ◽  
Author(s):  
Dang-Dang Li ◽  
Liang Yue ◽  
Zhan-Qing Yang ◽  
Lian-Wen Zheng ◽  
Bin Guo
Keyword(s):  
Stromal Cells ◽  
Physiological Function ◽  
Embryo Implantation ◽  
Differentiation Markers ◽  
Mouse Uterus ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Implantation Sites ◽  
Implantation Period

Background/Aims: Hmgn2 is involved in regulating embryonic development, but its physiological function during embryo implantation and decidualization remains unknown. Methods: In situ hybridization, real-time PCR, RNA interference, gene overexpression and MTS assay were used to examine the expression of Hmgn2 in mouse uterus during the pre-implantation period and explore its function and regulatory mechanisms in epithelial adhesion junction and stromal cell proliferation and differentiation. Results: Hmgn2 was primarily accumulated in uterine luminal epithelia on day 4 of pregnancy and subluminal stromal cells around the implanting blastocyst at implantation sites on day 5. Similar results were observed during delayed implantation and activation. Meanwhile, Hmgn2 expression was visualized in the decidua. In uterine epithelial cells, silencing of Hmgn2 by specific siRNA reduced the expression of adhesion molecules Cdh1, Cdh2 and Ctnnb1 and enhanced the expression of Muc1, whereas constitutive activation of Hmgn2 exhibited the opposite effects, suggesting a role for Hmgn2 in attachment reaction during embryo implantation. Estrogen stimulated the expression of Hmgn2 in uterine epithelia, but the stimulation was abrogated by ER antagonist ICI 182,780. Further analysis evidenced that attenuation of Hmgn2 might eliminate the regulation of estrogen on the expression of Cdh1, Cdh2 and Ctnnb1. In uterine stromal cells, progesterone induced the accumulation of Hmgn2 which advanced the expression of Prl8a2 and Prl3c1, two well-known differentiation markers for decidualization, but did not affect the proliferation of stromal cells. Knockdown of Hmgn2 blocked the progesterone-induced differentiation of uterine stromal cells. Moreover, Hmgn2 might serve as an intermediate to mediate the regulation of progesterone on Hand2. Conclusion: Hmgn2 may play an important role during embryo implantation and decidualization.

Differentially Expressed miRNAs in Mouse Uterus during Embryo Implantation

2020 ◽  
Author(s):  
Dingren Cao ◽  
Jingjie Liang ◽  
Lijun Liu ◽  
Xiaowei Zhang ◽  
Shuang Shi ◽  
...  
Keyword(s):  
Posttranscriptional Regulation ◽  
Transcriptome Sequencing ◽  
Embryo Implantation ◽  
Enrichment Analysis ◽  
Negative Control ◽  
Differentially Expressed ◽  
Mouse Uterus ◽  
Differentially Expressed Mirnas ◽  
Implantation Sites ◽  
Sequencing Result

Background: MicroRNAs (miRNAs) play key roles in posttranscriptional regulation during the window of implantation. However, which miRNA may play regulatory role during the window of implantation remains to be studied in depth. This paper aimed to explore the miRNAs that played regulatory roles during the process of implantation. Methods: RNA sequencing was performed to analyze mice uterus tissue in gestation day 1 (D1), gestation day 4 (D4) and gestation day5 (D5). The tissues in D5 were divided into embryo implantation sites (D5IMS) and inter-implantation sites (D5IIS). The differentially expressed miRNAs were screened and bioinformatics analyzed. Transfecting miR-183-5p mimics into HEC-1-A cells, genes regulated by miR-183-5p were analyzed by transcriptome sequencing. Result: Eleven differentially expressed miRNAs were identified during the window of implantation. KEGG enrichment analysis showed that the most differentially expressed miRNAs mainly related to binding and signaling transduction related pathways. Especially miR-183-5p, miR-182-5p, miR-199b-5p and miR-218-5p play a crucial role in regulating many important pathways. Transcriptome sequencing results showed that there were 19 up-regulated and 31 down-regulated genes in the miR-183-5p mimics group compared with the negative control (NC) group. This work laid a foundation for the study of miRNA in early pregnancy.

scholarly journals Expression of DNA methyltransferases in the mouse uterus during early pregnancy and susceptibility to dietary folate deficiency

Reproduction ◽  
2012 ◽  
Vol 144 (1) ◽  
pp. 91-100 ◽  
Author(s):  
Y B Ding ◽  
J L He ◽  
X Q Liu ◽  
X M Chen ◽  
C L Long ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Embryo Implantation ◽  
Dna Methyltransferases ◽  
Deficient Diet ◽  
Mouse Uterus ◽  
Dietary Folate ◽  
Endometrial Cells ◽  
Pregnant Mice ◽  
Implantation Sites ◽  
Significant Expression

We have characterized the uterine expression of DNA methyltransferases (DNMTs) during early pregnancy in mice and determined whether a folate-deficient diet (FDD) can affect DNMTs in this context. Within endometrial cells, expressions of DNMT (cytosine-5) 1 (Dnmt1),Dnmt3a, andDnmt3bwere significantly elevated during the prereceptive phase of pregnancy but generally returned to baseline levels during receptive and postimplantation periods. As such, the transcription of DNMT genes is temporally regulated during early pregnancy. When comparisons were made between implantation sites (IS) and inter-IS on day 5 of pregnancy, lower levels ofDnmt3awere detected at IS. Comparisons between IS and inter-IS did not reveal significant expression differences for other DNMT genes. When tissue sections were examined, DNMT3A was specifically lower in the stroma of IS. Reduced DNMT1 and DNMT3B levels were also observed in the luminal and glandular epithelia of IS, whereas no obvious differences in the stroma were detected. In pseudo-pregnant mice subjected to a FDD, levels ofDnmt1andDnmt3a(but notDnmt3b) were significantly upregulated in endometrial tissues, as compared with controls. When tissues from these folate-deficient mice were examined, DNMT1 levels were elevated in both the luminal and glandular epithelia, whereas DNMT3A was upregulated in the luminal epithelium and the stroma. A slight increase in DNMT3B levels was detected in the glandular epithelium. These results indicate that DNMTs may regulate the transcription of endometrial genes associated with embryo implantation and that levels of DNMTs are affected by dietary folate in mice.

Expression of the novel gene embryo implantation factor 2 (EMO2) in the mouse uterus at the implantation sites

2009 ◽  
Vol 91 (5) ◽  
pp. 2116-2122 ◽  
Author(s):  
Zhaogui Sun ◽  
Renwei Su ◽  
Zengming Yang ◽  
Huijuan Shi ◽  
Chengquan Liu ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
The Novel ◽  
Mouse Uterus ◽  
Novel Gene ◽  
Implantation Sites

scholarly journals Polyamines Are Essential in Embryo Implantation: Expression and Function of Polyamine-Related Genes in Mouse Uterus during Peri-Implantation Period

Endocrinology ◽  
2008 ◽  
Vol 149 (5) ◽  
pp. 2325-2332 ◽  
Author(s):  
Yue-Chao Zhao ◽  
Yu-Jing Chi ◽  
Yong-Sheng Yu ◽  
Ji-Long Liu ◽  
Ren-Wei Su ◽  
...  
Keyword(s):  
Embryo Implantation ◽  
Mouse Uterus ◽  
Adenosylmethionine Decarboxylase ◽  
Polyamine Level ◽  
Coordinated Expression ◽  
Cell Growth And Differentiation ◽  
Implantation Sites ◽  
And Function ◽  
Post Implantation ◽  
Implantation Period

Polyamines are key regulators in cell growth and differentiation. It has been shown that ornithine decarboxylase (Odc) was essential for post-implantation embryo development, and overexpression of spermidine/spermine N1-acetyltransferase will lead to ovarian hypofunction and hypoplastic uteri. However, the expression and function of polyamine-related genes in mouse uterus during early pregnancy are still unknown. In this study we investigated the expression, regulation, and function of polyamine-related genes in mouse uterus during the peri-implantation period. Odc expression was strongly detected at implantation sites and stimulated by estrogen treatment. The expression of Odc antizyme 1 and spermidine/spermine N1-acetyltransferase was also highly shown at implantation sites and regulated by Odc or polyamine level in uterine cells. Embryo implantation was significantly inhibited by α-difluoromethylornithine, an Odc inhibitor. Moreover, the reduction of Odc activity caused by α-difluoromethylornithine treatment was compensated by the up-regulation of S-adenosylmethionine decarboxylase gene expression. Collectively, our results indicated that the coordinated expression of uterine polyamine-related genes may be important for embryo implantation.

scholarly journals Expression of corticotrophin-releasing hormone in the mouse uterus: participation in embryo implantation

1999 ◽  
Vol 163 (2) ◽  
pp. 221-227 ◽  
Author(s):  
I Athanassakis ◽  
V Farmakiotis ◽  
I Aifantis ◽  
A Gravanis ◽  
S Vassiliadis
Keyword(s):  
Cell Culture ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
Pregnant Uterus ◽  
Cell Culture Techniques ◽  
Releasing Hormone ◽  
Culture Techniques ◽  
Blastocyst Implantation ◽  
Implantation Sites

The detection of corticotropin-releasing hormone (CRH) in the pregnant and non-pregnant uterus has driven research to determine the role of this 41 amino acid neuropeptide in the female reproductive system. As concentrations of CRH mRNA and its peptide product are greater in the implantation sites of the early pregnant uterus compared with the regions between implantation sites, CRH has been hypothesised to participate in blastocyst implantation. Using the mouse system as an experimental model, we studied the distribution of CRH in the uterus during the oestrus cycle and early gestational period, and now provide evidence for its involvement in embryo implantation using cell culture techniques. The percentage of CRH-positive uterine cells and the amount of CRH released during anoestrus, pro-oestrus and oestrus were determined by immunofluorescence and ELISA experiments respectively. The highest number of intracellularly CRH-positive cells was obtained during pro-oestrus, whereas the highest CRH concentration in uterine cell culture supernatants was detected during anoestrus. At early stages of gestation, CRH was detected in the endometrium on days 2, 3 and 4 of pregnancy and in the myometrium on days 3 and 4, whereas it was undetectable on day 5. The functional role of CRH during early gestation was evaluated by administering anti-CRH antibody to mice from day 3 to day 8 of pregnancy. This treatment resulted in implantation failure in 60% of the cases, in which implantation sites, although clearly present in the uterus, had failed to host an embryo. These results provide direct evidence about the involvement of CRH in murine embryo implantation and are in agreement with hypotheses postulated in humans.

Inhibition of TMEM16A impedes embryo implantation and decidualization in mice

Reproduction ◽  
2018 ◽  
Author(s):  
Qianrong Qi ◽  
Yifan Yang ◽  
Kailin Wu ◽  
Qingzhen Xie
Keyword(s):  
Progesterone Receptor ◽  
Stromal Cells ◽  
Embryo Implantation ◽  
Mouse Uterus ◽  
Endometrial Stromal Cells ◽  
Uterine Endometrium ◽  
Molecule Inhibitor ◽  
Pathway Inhibition ◽  
And Function ◽  
Reproductive Processes

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization, and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is up-regulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.

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