scholarly journals Inhibition of DRP1 Impedes Zygotic Genome Activation and Preimplantation Development in Mice

2021 ◽  
Vol 9 ◽  
Author(s):  
Yuanyuan Li ◽  
Ning-Hua Mei ◽  
Gui-Ping Cheng ◽  
Jing Yang ◽  
Li-Quan Zhou
Keyword(s):  
Embryo Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryos ◽  
Dependent Manner ◽  
Zygotic Genome Activation ◽  
Preimplantation Embryo Development ◽  
Cell Embryo ◽  
Embryo Stage ◽  
Genome Activation ◽  
Zygotic Genome

Mitochondrion plays an indispensable role during preimplantation embryo development. Dynamic-related protein 1 (DRP1) is critical for mitochondrial fission and controls oocyte maturation. However, its role in preimplantation embryo development is still lacking. In this study, we demonstrate that inhibition of DRP1 activity by mitochondrial division inhibitor-1, a small molecule reported to specifically inhibit DRP1 activity, can cause severe developmental arrest of preimplantation embryos in a dose-dependent manner in mice. Meanwhile, DRP1 inhibition resulted in mitochondrial dysfunction including decreased mitochondrial activity, loss of mitochondrial membrane potential, reduced mitochondrial copy number and inadequate ATP by disrupting both expression and activity of DRP1 and mitochondrial complex assembly, leading to excessive ROS production, severe DNA damage and cell cycle arrest at 2-cell embryo stage. Furthermore, reduced transcriptional and translational activity and altered histone modifications in DRP1-inhibited embryos contributed to impeded zygotic genome activation, which prevented early embryos from efficient development beyond 2-cell embryo stage. These results show that DRP1 inhibition has potential cytotoxic effects on mammalian reproduction, and DRP1 inhibitor should be used with caution when it is applied to treat diseases. Additionally, this study improves our understanding of the crosstalk between mitochondrial metabolism and zygotic genome activation.

Expression and localization of Nlrp4g in mouse preimplantation embryo

Zygote ◽  
2014 ◽  
Vol 23 (6) ◽  
pp. 846-851 ◽  
Author(s):  
Hui Peng ◽  
Xiujiao Lin ◽  
Wenhao Li ◽  
Wenchang Zhang
Keyword(s):  
Preimplantation Embryo ◽  
Expression Patterns ◽  
Blastocyst Stage ◽  
Preimplantation Embryo Development ◽  
Gene Copies ◽  
Mouse Preimplantation Embryo ◽  
Cell Embryo ◽  
Embryo Stage ◽  
Genome Activation ◽  
Zygotic Genome

SummaryThe Nlrp gene family contains 20 members and plays a pivotal role in the innate immune and reproductive systems in the mouse. During evolution, seven Nlrp4 gene copies (named from Nlrp4a to Nlrp4g). Nlrp4a–Nlrp4g have arisen that display specific or preferential ovarian expression patterns. However, the expression pattern and localization of Nlrp4g in mouse preimplantation embryo development are unknown. Here we report that Nlrp4g was highly expressed in mature oocytes and zygotes, then downregulated and not detected after the 2-cell embryo stage. NLRP4G protein remained present through the blastocyst stage and was mainly localized in the cytoplasm. Furthermore, overexpression of Nlrp4g in zygotes did not affect normal development in terms of the rate of blastocyst formation. These results provide the first evidence that NLRP4G is a maternal factor that may play essential role during zygotic genome activation in the mouse.

scholarly journals DPPA2 and DPPA4 are dispensable for mouse zygotic genome activation and preimplantation development

2021 ◽  
Author(s):  
Zhiyuan Chen ◽  
Zhenfei Xie ◽  
Yi Zhang
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Embryonic Stem ◽  
Preimplantation Development ◽  
Dependent Manner ◽  
Maternal Factors ◽  
Zygotic Genome Activation ◽  
Cell Embryo ◽  
Genome Activation ◽  
Zygotic Genome

How maternal factors in oocytes initiate zygotic genome activation (ZGA) remains elusive. Recent studies indicate that DPPA2 and DPPA4 are required for establishing a 2-cell embryo-like (2C-like) state in mouse embryonic stem cells (ESCs) in a DUX-dependent manner. These results suggest that DPPA2 and DPPA4 are essential maternal factors that regulate Dux and ZGA in embryos. By analyzing maternal knockout and maternal-zygotic knockout embryos, we unexpectedly found that Dux activation, ZGA, and preimplantation development are normal in embryos without DPPA2 or DPPA4. Thus, unlike in ESCs/2C-like cells, DPPA2 and DPPA4 are dispensable for ZGA and preimplantation development.

scholarly journals Phosphatidylinositol 3-kinase signaling in mammalian preimplantation embryo development

Reproduction ◽  
2008 ◽  
Vol 136 (2) ◽  
pp. 147-156 ◽  
Author(s):  
Chris O'Neill
Keyword(s):  
Embryo Development ◽  
Normal Development ◽  
Preimplantation Embryo ◽  
Preimplantation Embryos ◽  
External Information ◽  
Ph Domain ◽  
Phosphatidylinositol 3 Kinase ◽  
Preimplantation Embryo Development ◽  
Wide Range ◽  
Phosphatidylinositol 3

The development of the preimplantation mammalian embryo is an autopoietic process; once initiated development proceeds without an absolute requirement for external information or growth cues. This developmental autonomy is partly explained by the generation of autocrine trophic ligands that are released and act back on the embryo via specific receptors. Several embryotrophic ligands cause receptor-dependent activation of 1-o-phosphatidylinositol 3-kinase. This enzyme phosphorylates phosphatidylinositol-4,5-bisphosphate to form phosphatidylinositol-3,4,5-trisphosphate. Genetic or pharmacological ablation of this enzyme activity disrupts normal development of preimplantation embryos. Phosphatidylinositol-3,4,5-trisphosphate is a membrane lipid that acts as a docking site for a wide range of proteins possessing the pleckstrin homology (PH) domain. Such proteins are important regulators of cell survival, proliferation, and differentiation. RAC-α serine/threonine protein kinase is an important PH domain protein and its activity is required for normal preimplantation embryo development and survival. The activity of a range of PH domain proteins is also implicated in the normal development of the embryo. This review critically examines the evidence for the activation of 1-o-phosphatidylinositol 3-kinase in the generation of pleiotypic trophic response to embryotrophins in the autopoietic development of the preimplantation embryo.

scholarly journals Intracellular oxygen metabolism during bovine oocyte and preimplantation embryo development

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Paul J. McKeegan ◽  
Selina F. Boardman ◽  
Amy A. Wanless ◽  
Grace Boyd ◽  
Laura J. Warwick ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Oxygen Consumption ◽  
Oxygen Concentration ◽  
Embryo Development ◽  
Preimplantation Embryo ◽  
Complex Iii ◽  
Preimplantation Embryos ◽  
Mitochondrial Oxygen Consumption ◽  
Preimplantation Embryo Development

AbstractWe report a novel method to profile intrcellular oxygen concentration (icO2) during in vitro mammalian oocyte and preimplantation embryo development using a commercially available multimodal phosphorescent nanosensor (MM2). Abattoir-derived bovine oocytes and embryos were incubated with MM2 in vitro. A series of inhibitors were applied during live-cell multiphoton imaging to record changes in icO2 associated with mitochondrial processes. The uncoupler carbonyl cyanide-p-trifluoromethoxyphenylhydrazone (FCCP) uncouples mitochondrial oxygen consumption to its maximum, while antimycin inhibits complex III to ablate mitochondrial oxygen consumption. Increasing oxygen consumption was expected to reduce icO2 and decreasing oxygen consumption to increase icO2. Use of these inhibitors quantifies how much oxygen is consumed at basal in comparison to the upper and lower limits of mitochondrial function. icO2 measurements were compared to mitochondrial DNA copy number analysed by qPCR. Antimycin treatment increased icO2 for all stages tested, suggesting significant mitochondrial oxygen consumption at basal. icO2 of oocytes and preimplantation embryos were unaffected by FCCP treatment. Inner cell mass icO2 was lower than trophectoderm, perhaps reflecting limitations of diffusion. Mitochondrial DNA copy numbers were similar between stages in the range 0.9–4 × 106 copies and did not correlate with icO2. These results validate the MM2 probe as a sensitive, non-toxic probe of intracellular oxygen concentration in mammalian oocytes and preimplantation embryos.

scholarly journals Pleomorphic Adenoma Gene 1 Is Needed For Timely Zygotic Genome Activation and Early Embryo Development

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Elo Madissoon ◽  
Anastasios Damdimopoulos ◽  
Shintaro Katayama ◽  
Kaarel Krjutškov ◽  
Elisabet Einarsdottir ◽  
...  
Keyword(s):  
Pleomorphic Adenoma ◽  
Embryo Development ◽  
Early Embryo ◽  
Zygotic Genome Activation ◽  
Early Embryo Development ◽  
Genome Activation ◽  
Zygotic Genome

MiR-290 family maintains developmental potential by targeting p21 in mouse pre-implantation embryos

2021 ◽  
Author(s):  
Xiangnan Li ◽  
Yueshi Liu ◽  
Qier Mu ◽  
Junliang Tian ◽  
Haiquan Yu
Keyword(s):  
Embryonic Development ◽  
Untranslated Region ◽  
Target Genes ◽  
Embryonic Stem ◽  
Blastocyst Stage ◽  
Developmental Potential ◽  
Cell Embryo ◽  
Embryo Stage ◽  
Genome Activation ◽  
Zygotic Genome

Abstract The miR-290 family is a mouse-specific microRNA cluster, which maintains mouse embryonic stem cells (ESCs) pluripotency by increasing OCT3/4 and C-MYC expression. However, its functions in mouse pre-implantation embryos remain unclear, especially during zygotic genome activation (ZGA). In this study, miR-290 family expression increased from the two-cell embryo stage through the blastocyst stage. Inhibition of miR-294-3p/5p did not affect ZGA initiation or embryo development, whereas pri-miR-290 knockdown decreased ZGA gene expression and slowed embryonic development. In addition, pluripotency decreased in ESCs derived from pri-miR-290 knockdown blastocysts. To clarify the mechanism of action, 33 candidate miR-294-3p target genes were screened from three databases, and miR-294-3p directly targeted the 3′-untranslated region of Cdkn1a (p21) mRNA. Similar to pri-miR-290 knockdown, P21 overexpression impeded embryonic development, whereas simultaneous overexpression of P21 and pri-miR-290 partially rescued embryonic development. The results indicate that the miR-290 family participates in promoting ZGA process and maintaining developmental potency in embryos by targeting p21.

scholarly journals Dynamics of TET family expression in porcine preimplantation embryos is related to zygotic genome activation and required for the maintenance of NANOG

2014 ◽  
Vol 386 (1) ◽  
pp. 86-95 ◽  
Author(s):  
Kiho Lee ◽  
Jennifer Hamm ◽  
Kristin Whitworth ◽  
Lee Spate ◽  
Kwang-wook Park ◽  
...  
Keyword(s):  
Preimplantation Embryos ◽  
Zygotic Genome Activation ◽  
Genome Activation ◽  
Zygotic Genome

scholarly journals Functions and Regulation of Endogenous Retrovirus Elements during Zygotic Genome Activation: Implications for Improving Somatic Cell Nuclear Transfer Efficiency

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 829
Author(s):  
Bo Fu ◽  
Hong Ma ◽  
Di Liu
Keyword(s):  
Somatic Cell ◽  
Gene Regulatory Network ◽  
Regulatory Network ◽  
Somatic Cell Nuclear Transfer ◽  
Nuclear Transfer ◽  
Preimplantation Embryos ◽  
Zygotic Genome Activation ◽  
Gene Regulatory ◽  
Genome Activation ◽  
Zygotic Genome

Endogenous retroviruses (ERVs), previously viewed as deleterious relics of ancestral retrovirus infections, are silenced in the vast majority of cells to minimize the risk of retrotransposition. Counterintuitively, bursts of ERV transcription usually occur during maternal-to-zygotic transition (MZT) in preimplantation embryos; this is regarded as a major landmark event in the zygotic genome activation (ZGA) process, indicating that ERVs play an active part in ZGA. Evolutionarily, the interaction between ERVs and hosts is mutually beneficial. The endogenization of retrovirus sequences rewires the gene regulatory network during ZGA, and ERV repression may lower germline fitness. Unfortunately, owing to various limitations of somatic cell nuclear transfer (SCNT) technology, both developmental arrest and ZGA abnormalities occur in a high percentage of cloned embryos, accompanied by ERV silencing, which may be caused by the activation failure of upstream ERV inducers. In this review, we discuss the functions and regulation of ERVs during the ZGA process and the feasibility of temporal control over ERVs in cloned embryos via exogenous double homeobox (DUX). We hypothesize that further accurate characterization of the ERV-rewired gene regulatory network during ZGA may provide a novel perspective on the development of preimplantation embryos.

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