Mysteries in embryonic development: How can errors arise so frequently at the beginning of mammalian life?

Schneider, Isabell; Ellenberg, Jan

doi:10.1371/journal.pbio.3000173

Cited by 22 publications

(19 citation statements)

References 77 publications

(88 reference statements)

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“…However, PLK4 polymorphisms alone cannot explain the high prevalence of mosaicism in human embryos. Thus, the causes for the high mitotic error rates in human preimplantation embryos are still largely unknown (6,18,19).…”

Section: One Sentence Summary: Dna Damage In Sperm Cells Leads To Genmentioning

confidence: 99%

Sperm DNA damage causes genomic instability in early embryonic development

Middelkamp

Tol

Spierings

et al. 2019

Preprint

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AbstractGenomic instability is common in early embryo development, but the underlying causes are largely unknown. Here we examined the consequences of sperm DNA damage on the embryonic genome by single-cell genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by radiation. Sperm DNA damage caused fragmentation of chromosomes and segregation errors such as heterogoneic cell divisions yielding a broad spectrum of genomic aberrations that are similar to those frequently found in human embryos. The mosaic aneuploidies, mixoploidy, uniparental disomies and de novo structural variation induced upon sperm DNA damage may compromise health and lead to rare genomic disorders when embryos escape developmental arrest.One Sentence SummaryDNA damage in sperm cells leads to genomic defects in embryos

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Section: One Sentence Summary: Dna Damage In Sperm Cells Leads To Genmentioning

confidence: 99%

Sperm DNA damage causes genomic instability in early embryonic development

Middelkamp

Tol

Spierings

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Thus, genetically distinct cell lineages within an embryo can participate in development and contribute to disease. Despite the immediate relevance for human health and fertility, the causes for the high mitotic error rates in human preimplantation embryos are largely unknown (5,13). Mosaicism is prevalent in human spontaneous abortions of natural pregnancies (14), indicating that the causes for the high mitotic error rate in embryos are unrelated to the IVF procedures such as the ovarian stimulation regime, fluctuations in oxygen tension or temperature, and composition of the culture medium (15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Sperm DNA damage causes genomic instability in early embryonic development

et al. 2020

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Genomic instability is common in human embryos, but the underlying causes are largely unknown. Here, we examined the consequences of sperm DNA damage on the embryonic genome by single-cell whole-genome sequencing of individual blastomeres from bovine embryos produced with sperm damaged by γ-radiation. Sperm DNA damage primarily leads to fragmentation of the paternal chromosomes followed by random distribution of the chromosomal fragments over the two sister cells in the first cell division. An unexpected secondary effect of sperm DNA damage is the induction of direct unequal cleavages, which include the poorly understood heterogoneic cell divisions. As a result, chaotic mosaicism is common in embryos derived from fertilizations with damaged sperm. The mosaic aneuploidies, uniparental disomies, and de novo structural variation induced by sperm DNA damage may compromise fertility and lead to rare congenital disorders when embryos escape developmental arrest.

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“…In bovine embryos, like in humans, the centriole is carried by the sperm and inherited after subsequent division (52). It has been hypothesized that damaged or otherwise defective centrioles can block an embryo from developing (56). In our images, the centriole structure is included in the dry mass of the head.…”

Section: Discussionmentioning

confidence: 99%

Reproductive outcomes predicted by phase imaging with computational specificity of spermatozoon ultrastructure

Kandel

Rubessa

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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The ability to evaluate sperm at the microscopic level, at high-throughput, would be useful for assisted reproductive technologies (ARTs), as it can allow specific selection of sperm cells for in vitro fertilization (IVF). The tradeoff between intrinsic imaging and external contrast agents is particularly acute in reproductive medicine. The use of fluorescence labels has enabled new cell-sorting strategies and given new insights into developmental biology. Nevertheless, using extrinsic contrast agents is often too invasive for routine clinical operation. Raising questions about cell viability, especially for single-cell selection, clinicians prefer intrinsic contrast in the form of phase-contrast, differential-interference contrast, or Hoffman modulation contrast. While such instruments are nondestructive, the resulting image suffers from a lack of specificity. In this work, we provide a template to circumvent the tradeoff between cell viability and specificity by combining high-sensitivity phase imaging with deep learning. In order to introduce specificity to label-free images, we trained a deep-convolutional neural network to perform semantic segmentation on quantitative phase maps. This approach, a form of phase imaging with computational specificity (PICS), allowed us to efficiently analyze thousands of sperm cells and identify correlations between dry-mass content and artificial-reproduction outcomes. Specifically, we found that the dry-mass content ratios between the head, midpiece, and tail of the cells can predict the percentages of success for zygote cleavage and embryo blastocyst formation.

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Mysteries in embryonic development: How can errors arise so frequently at the beginning of mammalian life?

Cited by 22 publications

References 77 publications

Sperm DNA damage causes genomic instability in early embryonic development

Sperm DNA damage causes genomic instability in early embryonic development

Sperm DNA damage causes genomic instability in early embryonic development

Reproductive outcomes predicted by phase imaging with computational specificity of spermatozoon ultrastructure

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