New insights into the role of centrosomes in mammalian fertilization and implications for ART

Schatten, Heide; Sun, Qing‐Yuan

doi:10.1530/rep-11-0261

Cited by 47 publications

(26 citation statements)

References 61 publications

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“…The embryonic arrest we observe may be because much of the maternal Asl is unavailable after fertilization. This is consistent with the idea that the loss of centrosomal proteins inactivates the paternal centrosome until it recruits maternal centrosomal proteins in the zygote and at the appropriate time [33, 34]. Nonetheless, excess paternal Asl interferes with zygotic aster formation.…”

Section: Resultssupporting

confidence: 88%

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

et al. 2015

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SUMMARY Centrosome reduction is the decrease in centrosomal components during spermatid differentiation (spermiogenesis) [1, 2]. It is one of several dramatic subcellular reorganizations that leads to spermatozoa formation common to a wide range of animals [3]. However, the mechanism underlying centrosome reduction is unknown and its functions are unclear. Here, we show that in Drosophila melanogaster spermiogenesis, the quantity of centrosomal proteins is dramatically reduced [4, 5];for example, Asterless (Asl) is reduced ~500-fold and is barely detected in spermatozoa. Asl reduction is regulated through a subset of its domains by the master regulator of centriole duplication Plk4[6–8] and by the ubiquitin ligase that targets Plk4 for degradation: Slimb [9, 10]. When Asl reduction is attenuated by Asl overexpression, plk4 mutations, Plk4 RNAi, or Slimb overexpression, Asl levels are higher in spermatozoa, resulting in embryo’s with reduced viability. Significantly, overexpressing Plk4 and Asl simultaneously, or combining plk4 and slimb mutations, balances their opposing effects on Asl reduction, restoring seemingly normal fertility. This suggests that increased Asl levels cause the observed reduced fertility, and not other pleotropic effects. Attenuation of Asl reduction also causes delayed development and a failure to form astral microtubules in the zygote. Together, we provide the first insight into a molecular mechanism that regulates centrosome reduction and the first direct evidence that centrosome reduction is essential for postfertilization development.

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Section: Resultssupporting

confidence: 88%

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

et al. 2015

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“…In many species, the sperm contributes a centrosome to the resulting embryo at the time of fertilization as well as other essential components of the MTOC that attract proteins to this complex from the egg’s stores 128 , 129 . Experiments involving the fertilization of an egg with multiple sperm (i.e., polyspermy) have revealed the consequences of having multiple centrosomes in an early embryo; these embryos typically develop multiple cleavage furrows, distribute their chromosomes unevenly between blastomeres, and fail to develop beyond the early cleavage stages 76 , 130 .…”

Section: Introductionmentioning

confidence: 99%

It’s never too early to get it Right

Vandenberg

Lemire

Levin

2013

Communicative & Integrative Biology

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For centuries, scientists and physicians have been captivated by the consistent left-right (LR) asymmetry of the heart, viscera, and brain. A recent study implicated tubulin proteins in establishing laterality in several experimental models, including asymmetric chemosensory receptor expression in C. elegans neurons, polarization of HL-60 human neutrophil-like cells in culture, and asymmetric organ placement in Xenopus. The same mutations that randomized asymmetry in these diverse systems also affect chirality in Arabidopsis, revealing a remarkable conservation of symmetry-breaking mechanisms among kingdoms. In Xenopus, tubulin mutants only affected LR patterning very early, suggesting that this axis is established shortly after fertilization. This addendum summarizes and extends the knowledge of the cytoskeleton’s role in the patterning of the LR axis. Results from many species suggest a conserved role for the cytoskeleton as the initiator of asymmetry, and indicate that symmetry is first broken during early embryogenesis by an intracellular process.

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“…Two mechanisms may account for these abnormalities in 2PN zygotes: Dysfunctions of centrosome components in the sperm or oocyte (Schatten and Sun, , ; Alvarez Sedo et al, ) or impaired regulation of the centrosome cycle (Kalatova et al, ). The cell‐cycle regulation systems associated with centrosome duplication are not well understood in human embryos at the cleavage stage (Mantzouratou and Delhanty, ), although it is conceivable that additional rounds of centrosome duplication per cell cycle can produce supernumerary centrosomes (Srsen and Merdes, ), which would accumulate in early embryos during three cleavages.…”

Section: Discussionmentioning

confidence: 99%

Abnormalities in centrosome number in human embryos and embryonic stem cells

Ouyang

Dai

et al. 2016

Molecular Reproduction Devel

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Chromosomal abnormalities are common in human embryos. Previous studies have suggested links between centrosome number and chromosome abnormalities, but information regarding abnormalities in centrosome number in human embryos is limited. We analyzed abnormalities in centrosome number in human embryos and embryonic stem cells (hESCs). Following normal fertilization, supernumerary centrosomes were present at rates of 7.3% in two-pronucleus (2PN)-stage zygotes and 6.5% in first-cleavage zygotes. Supernumerary centrosomes were also detected in 24.4% of blastomeres from 60% of embryos derived from 2PN zygotes. Conversely, in mono- (1PN) and tri-pronucleus (3PN) zygotes, the frequency of abnormal centrosome number increased substantially at first cleavage. Rates in blastomeres of Day-3 embryos, however, were about the same between embryos derived from 1PN and 2PN zygotes, whereas abnormalities in centrosome number were higher in those from 3PN zygotes. By comparison, the rate of abnormal centrosome numbers in hESCs was 1.5-11.2%. Thus, abnormalities in centrosome number existed in human zygotes and cleaved embryos-especially those resulting from aberrant fertilization-but the frequency of such abnormalities was lower in hESCs derived from these embryos. These findings identify a source of the chromosomal instability in human embryos and hESCs, and highlight new safety issues for human assisted reproductive technology. Mol. Reprod. Dev. 83: 392-404, 2016. © 2016 Wiley Periodicals, Inc.

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New insights into the role of centrosomes in mammalian fertilization and implications for ART

Cited by 47 publications

References 61 publications

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila

It’s never too early to get it Right

Abnormalities in centrosome number in human embryos and embryonic stem cells

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