Effects of ERα-specific antagonist on mouse preimplantation embryo development and zygotic genome activation

Zhang, Yanqin; Jiang, Yonglei; Lian, Xiuli; Xu, Shunqing; Wei, Jianen; Chu, Chenfeng; Wang, Shie

doi:10.1016/j.jsbmb.2014.09.023

Cited by 10 publications

(19 citation statements)

References 34 publications

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“…The behavior of nuclear ER α was consistent with our previous observation that MPP treatment affected nuclear ER α expression in two‐cell embryos (Zhang et al . ). In order to confirm the specificity of MPP to ER α , MCF‐7 cells, which is ER α ‐positive breast cancer cells, were treated with different concentrations of MPP.…”

Section: Resultsmentioning

confidence: 97%

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Roles of ERα during mouse trophectoderm lineage differentiation: revealed by antagonist and agonist of ERα

Xiaoxiang

Song

et al. 2016

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During mouse early embryogenesis, blastomeres increase in number by the morula stage. Among them, the outer cells are polarized and differentiated into trophectoderm (TE), while the inner cells remain unpolarized and give rise to inner cell mass (ICM). TE provides an important liquid environment for ICM development. In spite of extensive research, the molecular mechanisms underlying TE formation are still obscure. In order to investigate the roles of estrogen receptor a (ERa) in this course, mouse 8-cell embryos were collected and cultured in media containing ERa specific antagonist MPP and/or agonist PPT. The results indicated that MPP treatment inhibits blastocyst formation in a dose-dependent manner, while PPT, at proper concentration, promotes the cavitation ratio of mouse embryos. Immunofluorescence staining results showed that MPP significantly decreased the nuclear expression of CDX2 in morula, but no significant changes of OCT4 were observed. Moreover, after MPP treatment, the expression levels of the genes related to TE specification, Tead4, Gata3 and Cdx2, were significantly reduced. Overall, these results indicated that ERa might affect mouse embryo cavitation by regulating TE lineage differentiation.

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Section: Resultsmentioning

confidence: 97%

“…The results indicated that ER α has a functional role in mouse ZGA (Zhang et al . ). Besides, the blastocyst formation of mouse embryos was blocked significantly after MPP treatment (Xu et al .…”

Section: Introductionmentioning

confidence: 97%

Roles of ERα during mouse trophectoderm lineage differentiation: revealed by antagonist and agonist of ERα

Xiaoxiang

Song

et al. 2016

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“…; Zhang et al . ). Thus, two Akt specific inhibitors API‐2 and MK2206 were employed in our study to uncover the relationship between ZGA and Akt in mouse preimplantation embryo.…”

Section: Discussionmentioning

confidence: 97%

“…; Zhang et al . ). The intact nuclear shape of the arrested embryos showed no sign of apoptosis and remained similar with that of the 2‐cell embryos in vivo (Figs and ), indicating that their following development beyond the 2‐cell stage was seriously blocked.…”

Section: Discussionmentioning

confidence: 97%

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Inhibition of phosphorylated Ser473‐Akt from translocating into the nucleus contributes to 2‐cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis

Chen

Lian

et al. 2016

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Phosphorylated Ser473-Akt (p-Ser473-Akt) is extensively studied as a correlate for the activity of Akt, which plays an important role in mouse oogenesis and preimplantation embryogenesis. However, little progress has been made about its effect on the mouse zygotic genome activation (ZGA) of 2-cell stage in mouse preimplantation embryos. In this study, we confirmed its localization in the pronuclei of 1-cell embryos and found that p-Ser473-Akt acquired prominent nucleus localization in 2-cell embryos physiologically. Akt specific inhibitors API-2 and MK2206 could inhibit the development of mouse preimplantation embryos in vitro, and induce 2-cell arrest at certain concentrations. 2-cell embryos exposed to 2.0 lmol/L API-2 or 30 lmol/L MK2206 displayed attenuated immunofluorescence intensity of p-Ser473-Akt in the nucleus. Simultaneously, qRT-PCR results revealed that 2.0 lmol/L API-2 treatment significantly downregulated the mRNA pattern of MuERV-L and eIF-1A, two marker genes of ZGA, suggesting a defect in ZGA compared with that of control group. Collectively, our work demonstrated the nuclear localization of p-Ser473-Akt during major ZGA, and Akt specific inhibitors API-2 and MK2206 which led to 2-cell arrest inhibited p-Ser473-Akt from translocating into the nucleus of 2-cell embryos with defective ZGA as well, implying p-Ser473-Akt may be a potential player in the major ZGA of 2-cell mouse embryos.

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RNA‐Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation

et al. 2019

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A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA‐binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf 2bp2 (also commonly known as Imp2 ) in mouse embryos causes early embryonic developmental arrest in vitro at the 2‐cell‐stage. Transcriptomics and proteomics analyses of 2‐cell‐stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14 , both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild‐type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10 −9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2‐treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development‐related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

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Effects of ERα-specific antagonist on mouse preimplantation embryo development and zygotic genome activation

Cited by 10 publications

References 34 publications

Roles of ERα during mouse trophectoderm lineage differentiation: revealed by antagonist and agonist of ERα

Roles of ERα during mouse trophectoderm lineage differentiation: revealed by antagonist and agonist of ERα

Inhibition of phosphorylated Ser473‐Akt from translocating into the nucleus contributes to 2‐cell arrest and defective zygotic genome activation in mouse preimplantation embryogenesis

RNA‐Binding Protein IGF2BP2/IMP2 is a Critical Maternal Activator in Early Zygotic Genome Activation

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