scholarly journals Growth Factors, and Cytokines; Understanding the Role of Tyrosine Phosphatase SHP2 in Gametogenesis and Early Embryo Development

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1798
Author(s):  
Muhammad Idrees ◽  
Seon-Hwa Oh ◽  
Tahir Muhammad ◽  
Marwa El-Sheikh ◽  
Seok-Hwan Song ◽  
...  
Keyword(s):  
Growth Factors ◽  
Growth Factor ◽  
Embryo Development ◽  
Tyrosine Phosphatase ◽  
Embryo Implantation ◽  
Early Embryo ◽  
Cellular Growth ◽  
Protein Signaling ◽  
Early Embryo Development ◽  
Multifunctional Protein

Growth factors and cytokines have vital roles in germ cell development, gamete maturation, and early embryo development. Cell surface receptors are present for growth factors and cytokines to integrate with and trigger protein signaling in the germ and embryo intracellular milieu. Src-homology-2-containing phosphotyrosine phosphatase (SHP2) is a ubiquitously expressed, multifunctional protein that plays a central role in the signaling pathways involved in growth factor receptors, cytokine receptors, integrins, and G protein-coupled receptors. Over recent decades, researchers have recapitulated the protein signaling networks that influence gamete progenitor specification as well as gamete differentiation and maturation. SHP2 plays an indispensable role in cellular growth, survival, proliferation, differentiation, and migration, as well as the basic events in gametogenesis and early embryo development. SHP2, a classic cytosolic protein and a key regulator of signal transduction, displays unconventional nuclear expression in the genital organs. Several observations provided shreds of evidence that this behavior is essential for fertility. The growth factor and cytokine-dependent roles of SHP2 and its nuclear/cytoplasmic presence during gamete maturation, early embryonic development and embryo implantation are fascinating and complex subjects. This review is intended to summarize the previous and recent knowledge about the SHP2 functions in gametogenesis and early embryo development.

P–181 Morphine regulates BMP4 growth factor and is involved in in-vitro early embryo development and PGCs formation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Muñoa ◽  
M Araolaza-Lasa ◽  
I Urizar-Arenaza ◽  
M Gianzo Citores ◽  
N Subiran Ciudad
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Environmental Factors ◽  
Embryo Development ◽  
Early Embryo ◽  
Epigenetic Changes ◽  
Morphine Treatment ◽  
Early Embryo Development

Abstract Study question To elucidate if morphine can alter embryo development. Summary answer Chronic morphine treatment regulates BMP4 growth factor, in terms of gene expression and H3K27me3 enrichment and promotes in-vitro blastocysts development and PGC formation. What is known already BMP4 is a member of the bone morphogenetic protein family, which acts mainly through SMAD dependent pathway, to play an important role in early embryo development. Indeed, BMP4 enhances pluripotency in mouse embryonic stem cells (mESCs) and, specifically, is involved in blastocysts formation and primordial germ cells (PGCs) generation. Although, external morphine influence has been previously reported on the early embryo development, focus on implantation and uterus function, there is a big concern in understanding how environmental factors can cause stable epigenetic changes, which could be maintained during development and lead to health problems. Study design, size, duration First, OCT4-reported mESCs were chronically treated with morphine during 24h, 10–5mM. After morphine removal, mESCs were collected for RNA-seq and H3K27me3 ChIP-seq study. To elucidate the role of morphine in early embryo development, two cell- embryos stage were chronically treated with morphine for 24h and in-vitro cultured up to the blastocyst stage in the absence of morphine. Furthermore, after morphine treatment mESCs were differentiated to PGCs, to elucidate the role of morphine in PGC differentiation. Participants/materials, setting, methods Transcriptomic analyses and H3K27me3 genome wide distribution were carried out by RNA-Sequencing and Chip-Sequencing respectively. Validations were performed by RNA-RT-qPCR and Chip-RT-qPCR. Main results and the role of chance Dynamic transcriptional analyses identified a total of 932 differentially expressed genes (DEGs) after morphine treatment on mESCs, providing strong evidence of a transcriptional epigenetic effect induced by morphine. High-throughput screening approaches showed up Bmp4 as one of the main morphine targets on mESCs. Morphine caused an up-regulation of Bmp4 gene expression together with a decrease of H3K27me3 enrichment at promoter level. However, no significant differences were observed on gene expression and H3K27me3 enrichment on BMP4 signaling pathway components (such as Smad1, Smad4, Smad5, Smad7, Prdm1 and Prmd14) after morphine treatment. On the other hand, the Bmp4 gene expression was also up-regulated in in-vitro morphine treated blastocyst and in-vitro morphine treated PGCs. These results were consistent with the increase in blastocyst rate and PGC transformation rate observed after morphine chronic treatment. Limitations, reasons for caution To perform the in-vitro analysis. Further studies are needed to describe the whole signaling pathways underlying BMP4 epigenetic regulation after morphine treatment. Wider implications of the findings: Our findings confirmed that mESCs and two-cell embryos are able to memorize morphine exposure and promote both blastocyst development and PGCs formation through potentially BMP4 epigenetic regulation. These results provide insights understanding how environmental factors can cause epigenetic changes during the embryo development, leading to alterations and producing health problems/diseases Trial registration number Not applicable

130. MICROARRAY ANALYSIS OF FOETAL MOUSE BRAIN FOLLOWING INDUCTION OF MITOCHONDRIAL DYSFUNCTION DURING PRE-IMPLANTATION EMBRYO DEVELOPMENT

2009 ◽  
Vol 21 (9) ◽  
pp. 49
Author(s):  
T. Fullston ◽  
M. Mitchell ◽  
S. Wakefield ◽  
A. Filby ◽  
M. Lane
Keyword(s):  
Gene Expression ◽  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Embryo Development ◽  
Epigenetic Modification ◽  
Gene Array ◽  
Early Embryo ◽  
Cellular Growth ◽  
Early Embryo Development ◽  
Foetal Brain

Environmental stress can disrupt mitochondrial function in the pre-implantation embryo, subsequently hindering embryo viability. Brain tissue is also sensitive to developmental perturbations, and we have previously discovered genes involved in neurological function and epigenetic modification are differentially expressed in blastocysts following mitochondrial dysfunction by amino-oxyacetate (AOA). In this study CBAxC57Bl6 2 cell stage mouse embryos were cultured in 5μM-AOA without pyruvate for 72h to induce mitochondrial dysfunction. Blastocyst stage embryos were then transferred to pseudopregnant recipients and the expression profile of day 18 foetal brains was interrogated using microarray. mRNA from mouse whole brain (4 per treatment) was extracted and analysed using an Affymetrix gene array. Ingenuity Pathway Analysis software identified persistent alterations in gene expression pathways in foetal brain after AOA treatment during embryo culture, that were subsequently confirmed by qPCR. Expression was significantly increased by both array and qPCR (>1.5 fold, p<0.05) for; 1) Eomes (1.9, 2.9 fold respectively), a T-box transcription factor involved in differentiation, cell death and development, 2) Nr4a3 (1.8, 2.2 fold respectively), a steroid hormone receptor and putative transcriptional activator and 3) Nola3 (1.7, 1.9 fold respectively), a small nucleolar ribonucleoprotein involved in rRNA processing. Neurological disease, behavioural disorders, carbohydrate metabolism, cellular growth and proliferation, cell death, DNA replication, recombination and repair pathways also showed altered gene expression (>1.25 fold). qPCR was performed on 28 genes exhibiting the greatest change in expression. 24/28 genes confirmed the array data, and of the 4 genes that did not; two had expression not detected by qPCR (Snhg1, Speer6-ps1), and two contradicted array results (Atp1b3 p=0.05, Stk38l p=0.06). This study links mitochondrial dysfunction during early embryo development and persistent molecular changes in the developing foetal brain. This indicates that insults incurred during early embryo development can cause permanent changes that we predict results from aberrant epigenetic modification.

P-181 Morphine regulates BMP4 growth factor and is involved in in-vitro early embryo development and PGCs formation

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Muñoa ◽  
M Araolaza-Lasa ◽  
I Urizar-Arenaza ◽  
M Gianzo Citores ◽  
N Subiran Ciudad
Keyword(s):  
Gene Expression ◽  
Growth Factor ◽  
Environmental Factors ◽  
Embryo Development ◽  
Early Embryo ◽  
Epigenetic Changes ◽  
Morphine Treatment ◽  
Early Embryo Development

Abstract Study question To elucidate if morphine can alter embryo development. Summary answer Chronic morphine treatment regulates BMP4 growth factor, in terms of gene expression and H3K27me3 enrichment and promotes in-vitro blastocysts development and PGC formation. What is known already BMP4 is a member of the bone morphogenetic protein family, which acts mainly through SMAD dependent pathway, to play an important role in early embryo development. Indeed, BMP4 enhances pluripotency in mouse embryonic stem cells (mESCs) and, specifically, is involved in blastocysts formation and primordial germ cells (PGCs) generation. Although, external morphine influence has been previously reported on the early embryo development, focus on implantation and uterus function, there is a big concern in understanding how environmental factors can cause stable epigenetic changes, which could be maintained during development and lead to health problems. Study design, size, duration First, OCT4-reported mESCs were chronically treated with morphine during 24h, 10-5mM. After morphine removal, mESCs were collected for RNA-seq and H3K27me3 ChIP-seq study. To elucidate the role of morphine in early embryo development, two cell- embryos stage were chronically treated with morphine for 24h and in-vitro cultured up to the blastocyst stage in the absence of morphine. Furthermore, after morphine treatment mESCs were differentiated to PGCs, to elucidate the role of morphine in PGC differentiation. Participants/materials, setting, methods Transcriptomic analyses and H3K27me3 genome wide distribution were carried out by RNA-Sequencing and Chip-Sequencing respectively. Validations were performed by RNA-RT-qPCR and Chip-RT-qPCR. Main results and the role of chance Dynamic transcriptional analyses identified a total of 932 differentially expressed genes (DEGs) after morphine treatment on mESCs, providing strong evidence of a transcriptional epigenetic effect induced by morphine. High-throughput screening approaches showed up Bmp4 as one of the main morphine targets on mESCs. Morphine caused an up-regulation of Bmp4 gene expression together with a decrease of H3K27me3 enrichment at promoter level. However, no significant differences were observed on gene expression and H3K27me3 enrichment on BMP4 signaling pathway components (such as Smad1, Smad4, Smad5, Smad7, Prdm1 and Prmd14) after morphine treatment. On the other hand, the Bmp4 gene expression was also up-regulated in in-vitro morphine treated blastocyst and in-vitro morphine treated PGCs. These results were consistent with the increase in blastocyst rate and PGC transformation rate observed after morphine chronic treatment. Limitations, reasons for caution To perform the in-vitro analysis. Further studies are needed to describe the whole signaling pathways underlying BMP4 epigenetic regulation after morphine treatment. Wider implications of the findings Our findings confirmed that mESCs and two-cell embryos are able to memorize morphine exposure and promote both blastocyst development and PGCs formation through potentially BMP4 epigenetic regulation. These results provide insights understanding how environmental factors can cause epigenetic changes during the embryo development, leading to alterations and producing health problems/diseases. Trial registration number not applicable

Minor Splicing Factors Zrsr1 and Zrsr2 Essential for Gametogenesis, Early Embryo Development and Conversion of Stem Cells into 2C-Like

2019 ◽  
Author(s):  
Isabel G&oacute;mez-Redondo ◽  
Priscila Ramos-Ibeas ◽  
Eva Pericuesta ◽  
Benjamín Planells ◽  
Raul Fernández-González ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryo Development ◽  
Early Embryo ◽  
Splicing Factors ◽  
Early Embryo Development

scholarly journals LIN28 coordinately promotes nucleolar/ribosomal functions and represses the 2C-like transcriptional program in pluripotent stem cells

2021 ◽  
Author(s):  
Zhen Sun ◽  
Hua Yu ◽  
Jing Zhao ◽  
Tianyu Tan ◽  
Hongru Pan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryo Development ◽  
Pluripotent Stem Cells ◽  
Rna Binding ◽  
Stem Cell Differentiation ◽  
Early Embryo ◽  
Transcriptional Program ◽  
Cell Stage ◽  
Early Embryo Development ◽  
Nucleolar Stress

AbstractLIN28 is an RNA binding protein with important roles in early embryo development, stem cell differentiation/reprogramming, tumorigenesis and metabolism. Previous studies have focused mainly on its role in the cytosol where it interacts with Let-7 microRNA precursors or mRNAs, and few have addressed LIN28’s role within the nucleus. Here, we show that LIN28 displays dynamic temporal and spatial expression during murine embryo development. Maternal LIN28 expression drops upon exit from the 2-cell stage, and zygotic LIN28 protein is induced at the forming nucleolus during 4-cell to blastocyst stage development, to become dominantly expressed in the cytosol after implantation. In cultured pluripotent stem cells (PSCs), loss of LIN28 led to nucleolar stress and activation of a 2-cell/4-cell-like transcriptional program characterized by the expression of endogenous retrovirus genes. Mechanistically, LIN28 binds to small nucleolar RNAs and rRNA to maintain nucleolar integrity, and its loss leads to nucleolar phase separation defects, ribosomal stress and activation of P53 which in turn binds to and activates 2C transcription factor Dux. LIN28 also resides in a complex containing the nucleolar factor Nucleolin (NCL) and the transcriptional repressor TRIM28, and LIN28 loss leads to reduced occupancy of the NCL/TRIM28 complex on the Dux and rDNA loci, and thus de-repressed Dux and reduced rRNA expression. Lin28 knockout cells with nucleolar stress are more likely to assume a slowly cycling, translationally inert and anabolically inactive state, which is a part of previously unappreciated 2C-like transcriptional program. These findings elucidate novel roles for nucleolar LIN28 in PSCs, and a new mechanism linking 2C program and nucleolar functions in PSCs and early embryo development.

scholarly journals Geminin deletion in mouse oocytes results in impaired embryo development and reduced fertility

2016 ◽  
Vol 27 (5) ◽  
pp. 768-775 ◽  
Author(s):  
Xue-Shan Ma ◽  
Fei Lin ◽  
Zhong-Wei Wang ◽  
Meng-Wen Hu ◽  
Lin Huang ◽  
...  
Keyword(s):  
Embryo Development ◽  
Primordial Follicle ◽  
Early Embryo ◽  
Cell Cycle Checkpoint ◽  
Low Fertility ◽  
Early Embryo Development ◽  
Damage Repair ◽  
Cycle Checkpoint ◽  
Oocyte Meiotic Maturation ◽  
Zygote Stage

Geminin controls proper centrosome duplication, cell division, and differentiation. We investigated the function of geminin in oogenesis, fertilization, and early embryo development by deleting the geminin gene in oocytes from the primordial follicle stage. Oocyte-specific disruption of geminin results in low fertility in mice. Even though there was no evident anomaly of oogenesis, oocyte meiotic maturation, natural ovulation, or fertilization, early embryo development and implantation were impaired. The fertilized eggs derived from mutant mice showed developmental delay, and many were blocked at the late zygote stage. Cdt1 protein was decreased, whereas Chk1 and H2AX phosphorylation was increased, in fertilized eggs after geminin depletion. Our results suggest that disruption of maternal geminin may decrease Cdt1 expression and cause DNA rereplication, which then activates the cell cycle checkpoint and DNA damage repair and thus impairs early embryo development.

scholarly journals The Potential Roles of the G1LEA and G3LEA Proteins in Early Embryo Development and in Response to Low Temperature and High Salinity in Artemia sinica

PLoS ONE ◽  
2016 ◽  
Vol 11 (9) ◽  
pp. e0162272 ◽  
Author(s):  
Wei Zhao ◽  
Feng Yao ◽  
Mengchen Zhang ◽  
Ting Jing ◽  
Shuang Zhang ◽  
...  
Keyword(s):  
Low Temperature ◽  
Embryo Development ◽  
High Salinity ◽  
Early Embryo ◽  
Artemia Sinica ◽  
Early Embryo Development

Early embryo development anomalies identified by time-lapse system: prevalence and impacting factors

2021 ◽  
Author(s):  
Xavier Ferraretto ◽  
Karima Hammas ◽  
Marie-Astrid Llabador ◽  
Solenne Gricourt ◽  
Julie Labrosse ◽  
...  
Keyword(s):  
Embryo Development ◽  
Time Lapse ◽  
Early Embryo ◽  
Early Embryo Development ◽  
Impacting Factors
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