Two mutations in TUBB8 cause developmental arrest in human oocytes and early embryos

Histone modifications regulate gene expression and development. To address how they are reprogrammed in human early development, we investigated key histone marks in human oocytes and early embryos. Unlike that in mouse oocytes, the permissive mark trimethylated histone H3 lysine 4 (H3K4me3) largely exhibits canonical patterns at promoters in human oocytes. After fertilization, prezygotic genome activation (pre-ZGA) embryos acquire permissive chromatin and widespread H3K4me3 in CpG-rich regulatory regions. By contrast, the repressive mark H3K27me3 undergoes global depletion. CpG-rich regulatory regions then resolve to either active or repressed states upon ZGA, followed by subsequent restoration of H3K27me3 at developmental genes. Finally, by combining chromatin and transcriptome maps, we revealed transcription circuitry and asymmetric H3K27me3 patterning during early lineage specification. Collectively, our data unveil a priming phase connecting human parental-to-zygotic epigenetic transition.

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Chromosome damage and early developmental arrest caused by the Rex element of Drosophila melanogaster.

Genetics ◽

10.1093/genetics/138.2.401 ◽

1994 ◽

Vol 138 (2) ◽

pp. 401-411 ◽

Cited By ~ 1

Author(s):

L G Robbins ◽

S Pimpinelli

Keyword(s):

Drosophila Melanogaster ◽

Ribosomal Dna ◽

Maternal Effect ◽

Cell Biology ◽

Chromosome Breakage ◽

Chromosome Damage ◽

Specific Chromosome ◽

Developmental Arrest ◽

Early Embryos ◽

Early Developmental

Abstract Rex (Ribosomal exchange) is a genetically identified repeated element within the ribosomal DNA (rDNA) of Drosophila melanogaster. Rex has a semidominant maternal effect that promotes exchange between and within rDNA arrays in the first few embryonic mitoses. Several of Rex's genetic properties suggest that its primary effect is rDNA-specific chromosome breakage that is resolved by recombination. We report here that rDNA crossovers are only a small, surviving minority of Rex-induced events. Cytology of embryos produced by Rex-homozygous females reveals obvious chromosome damage in at least a quarter of the embryos within the first three mitotic divisions. More than half of the embryos produced by Rex females die, and the developmental arrest is among the earliest reported for any maternal-effect lethal. The striking lethal phenotype suggests that embryos with early chromosome damage could be particularly fruitful subjects for analysis of the cell biology of early embryos.

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Small RNA expression and miRNA modification dynamics in human oocytes and early embryos

Genome Research ◽

10.1101/gr.268193.120 ◽

2021 ◽

Vol 31 (8) ◽

pp. 1474-1485

Author(s):

Pauliina Paloviita ◽

Christel Hydén-Granskog ◽

Dawit A. Yohannes ◽

Priit Paluoja ◽

Juha Kere ◽

...

Keyword(s):

Small Rna ◽

Rna Expression ◽

Human Oocytes ◽

Early Embryos

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Maternal spindle transfer overcomes embryo developmental arrest caused by ooplasmic defects in mice

eLife ◽

10.7554/elife.48591 ◽

2020 ◽

Vol 9 ◽

Cited By ~ 2

Author(s):

Nuno Costa-Borges ◽

Katharina Spath ◽

Irene Miguel-Escalada ◽

Enric Mestres ◽

Rosa Balmaseda ◽

...

Keyword(s):

High Efficiency ◽

Developmental Competence ◽

Developmental Potential ◽

Clinical Model ◽

Adult Age ◽

Mtdna Mutations ◽

Developmental Arrest ◽

Multiple Organs ◽

Early Embryos ◽

Maternal Spindle Transfer

The developmental potential of early embryos is mainly dictated by the quality of the oocyte. Here, we explore the utility of the maternal spindle transfer (MST) technique as a reproductive approach to enhance oocyte developmental competence. Our proof-of-concept experiments show that replacement of the entire cytoplasm of oocytes from a sensitive mouse strain overcomes massive embryo developmental arrest characteristic of non-manipulated oocytes. Genetic analysis confirmed minimal carryover of mtDNA following MST. Resulting mice showed low heteroplasmy levels in multiple organs at adult age, normal histology and fertility. Mice were followed for five generations (F5), revealing that heteroplasmy was reduced in F2 mice and was undetectable in the subsequent generations. This pre-clinical model demonstrates the high efficiency and potential of the MST technique, not only to prevent the transmission of mtDNA mutations, but also as a new potential treatment for patients with certain forms of infertility refractory to current clinical strategies.

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Domains of high-polarized and low-polarized mitochondria may occur in mouse and human oocytes and early embryos

Human Reproduction ◽

10.1093/humrep/17.2.393 ◽

2002 ◽

Vol 17 (2) ◽

pp. 393-406 ◽

Cited By ~ 187

Author(s):

J. Van Blerkom

Keyword(s):

Human Oocytes ◽

Early Embryos

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Mutations inTUBB8cause a multiplicity of phenotypes in human oocytes and early embryos

Journal of Medical Genetics ◽

10.1136/jmedgenet-2016-103891 ◽

2016 ◽

Vol 53 (10) ◽

pp. 662-671 ◽

Cited By ~ 40

Author(s):

Ruizhi Feng ◽

Zheng Yan ◽

Bin Li ◽

Min Yu ◽

Qing Sang ◽

...

Keyword(s):

Human Oocytes ◽

Early Embryos

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Wenshen Shengjing Decoction Improves Early Embryo Development by Maintaining Low H3K27me3 Levels in Sperm and Pronuclear Embryos of Spermatogenesis Impaired Mice

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2021/8035997 ◽

2021 ◽

Vol 2021 ◽

pp. 1-11

Author(s):

Yanmei Sun ◽

Fan Gao ◽

Da Xu ◽

Lei Lu ◽

Qianggen Chen ◽

...

Keyword(s):

Embryo Development ◽

Early Embryo ◽

Development Rate ◽

Epigenetic Changes ◽

Zygotic Genome Activation ◽

Arrest Rate ◽

Developmental Arrest ◽

Early Embryos ◽

Genome Activation ◽

Zygotic Genome

Many ingredients in Wenshen Shengjing Decoction (WSSJD) can cause epigenetic changes in the development of different types of cells. It is not yet known whether they can cause epigenetic changes in sperms or early embryos. Here, we investigated the role of WSSJD in epigenetic modifications of sperms or early embryos and early embryo development. A mouse model with spermatogenesis disorders was established with cyclophosphamide (CPA). WSSJD was administrated for 30 days. The male model mice after the treatment were mated with the female mice treated with superovulation. The embryo development rate of each stage was calculated. Immunofluorescence staining was used to detect the expression of H3K27me3 in sperm, pronuclear embryos, and 2-cell embryos. Western blotting was used to detect the expression of histone demethylase KDM6A and methyltransferase EZH2 in 2-cell embryos with developmental arrest. The expressions of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) in 2-cell embryos with developmental arrest were analyzed with qRT-PCR. Comparing with the control group, CPA destroyed the development of seminiferous epithelium, significantly increased the expression level of H3K27me3 in sperm, reduced the expression ratio of H3K27me3 in female and male pronuclei, delayed the development of 2-cell embryos, and increased the developmental arrest rate and degeneration rate of 2-cell embryos. Moreover, the expressions of EZH2 and H3K27me3 were significantly increased in the 2-cell embryos with developmental arrest, and the expression of zygotic genome activation genes (ZSCAN4, E1F1AX, HSPA1A, ERV4-2, and MYC) was significantly decreased. Compared with the CPA group, WSSJD promoted the development of seminiferous epithelium, maintained a low level of H3K27me3 modification in sperm and male pronucleus, significantly increased the development rate of 2-cell embryos and 3-4 cell embryos, and reduced the developmental arrest rate and degeneration rate of 2-cell embryos. WSSJD may promote early embryonic development by maintaining a low level of H3K27me3 modification in sperm and male pronucleus and regulating the zygotic genome activation in mice with spermatogenesis disorders induced by CPA.

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Human Blastocyst is Susceptible to SARS-CoV-2 Infection based on Protein Level Examination of Key Entry Factors in Human Oocytes and Early Embryos

10.21203/rs.3.rs-288745/v1 ◽

2021 ◽

Author(s):

xingping liu ◽

Bing-xin Ma ◽

Li-quan Zhou

Keyword(s):

Inner Cell Mass ◽

Expression Patterns ◽

Cell Mass ◽

Blastocyst Stage ◽

Preimplantation Embryos ◽

Key Factors ◽

Human Oocytes ◽

Human Blastocyst ◽

Early Embryos ◽

Two Factors

Abstract Objective ACE2, TMPRSS2 and NRP1 are key factors for SARS-CoV-2 infection. Here, we used immunofluorescence to examine the expression patterns of ACE2, TMPRSS2 and NRP1 in human oocytes and different stages of preimplantation embryos to investigated the susceptibility to be infected by SARS-CoV-2.Methods We collected human GV oocytes and different stages of early embryos donated by patients and then performed immunofluorescence followed by confocal microscopy for signals of ACE2, TMPRSS2 and NRP1 proteins in these oocytes and embryos.Results We found that ACE2 was abundant in both inner cell mass and trophectoderm at blastocyst stage, while TMPRSS2 was mainly enriched in trophectoderm. Both of the two factors had faint signal in cleavage embryos and oocytes. In contrast, NRP1 was barely detectable in oocytes or any stage of early embryos. Conclusion Taken together, we propose that human blastocysts, instead of human oocytes and other stages of early embryos, are susceptible to be infected by SARS-CoV-2. Therefore, specific attention should be paid to manipulation of human blastocysts in assisted reproductive technology.

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