The Experts below are selected from a list of 12804 Experts worldwide ranked by ideXlab platform
Barbara T Wakimoto - One of the best experts on this subject based on the ideXlab platform.
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the deadbeat Paternal Effect of uncapped sperm telomeres on cell cycle progression and chromosome behavior in drosophila melanogaster
Genetics, 2016Co-Authors: Takuo Yamaki, Glenn K Yasuda, Barbara T WakimotoAbstract:Telomere-capping complexes (TCCs) protect the ends of linear chromosomes from illegitimate repair and end-to-end fusions and are required for genome stability. The identity and assembly of TCC components have been extensively studied, but whether TCCs require active maintenance in nondividing cells remains an open question. Here we show that Drosophila melanogaster requires Deadbeat (Ddbt), a sperm nuclear basic protein (SNBP) that is recruited to the telomere by the TCC and is required for TCC maintenance during genome-wide chromatin remodeling, which transforms spermatids to mature sperm. Ddbt-deficient males produce sperm lacking TCCs. Their offspring delay the initiation of anaphase as early as cycle 1 but progress through the first two cycles. Persistence of uncapped Paternal chromosomes induces arrest at or around cycle 3. This early arrest can be rescued by selective elimination of Paternal chromosomes and production of gynogenetic haploid or haploid mosaics. Progression past cycle 3 can also occur if embryos have reduced levels of the maternally provided checkpoint kinase Chk2. The findings provide insights into how telomere integrity affects the regulation of the earliest embryonic cell cycles. They also suggest that other SNBPs, including those in humans, may have analogous roles and manifest as Paternal Effects on embryo quality.
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the Paternal Effect gene ms 3 sneaky is required for sperm activation and the initiation of embryogenesis in drosophila melanogaster
Developmental Biology, 1998Co-Authors: Karen R Fitch, Barbara T WakimotoAbstract:Abstract Although a large number of maternal factors are known to be essential for fertilization or the earliest stages of embryogenesis inDrosophila melanogaster, the role of Paternally supplied products is not clearly understood. Paternal Effect mutations provide a means to identify factors specifically required by the sperm after its entry into the egg. Here we describe the third strict Paternal Effect gene to be identified inDrosophila, ms(3)sneaky(snky), which defines the earliest developmental arrest phenotype so far described. Characterization of two independently isolatedsnkymutations showed that they affected male fertility, but not viability or female fertility. Cytological analyses showed that spermatogenesis proceeded normally insnkymales. However, thesnkydefect was evident after sperm entry into the egg;snkysperm did not undergo nuclear decondensation, form a functional male pronucleus, or initiate mitotic divisions in the egg. Immunolocalization of tubulin and Drosophila Centrosomin, a known centrosomal component, showed thatsnky-inseminated eggs failed to reconstitute a microtubule-organizing center. In addition,snkysperm chromatin retained the histochemical properties of mature sperm chromatin for several hours after sperm entry, showed reduced staining with membrane-impermeant nuclear dyes, and failed to replicate. We conclude that thesnky+product is required for the initial response of the sperm to cytoplasmic cues in the egg and for the subsequent initiation of embryogenesis inDrosophila. We suggest that all of thesnkydefects can be explained by the failure of the sperm plasma membrane to break down after entry into the egg.
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genetic characterization of ms 3 k81 a Paternal Effect gene of drosophila melanogaster
Genetics, 1995Co-Authors: Glenn K Yasuda, Gerold Schubiger, Barbara T WakimotoAbstract:The vast majority of known male sterile mutants of Drosophila melanogaster fail to produce mature sperm or mate properly. The ms(3) K81(1) mutation is one of a rare class of male sterile mutations in which sterility is caused by developmental arrest after sperm entry into the egg. Previous studies showed that males homozygous for the K81(1) mutation produce progeny that arrest at either of two developmental stages. Most embryos arrest during early nuclear cycles, whereas the remainder are haploid embryos that arrest at a later stage. This description of the mutant phenotype was based on the analysis of a single allele isolated from a natural population. It was therefore unclear whether this unique Paternal Effect phenotype reflected the normal function of the gene. The genetic analysis and initial molecular characterization of five new K81 mutations are described here. Hemizygous conditions and heteroallelic combinations of the alleles were associated with male sterility caused by defects in embryogenesis. No other mutant phenotypes were observed. Thus, the K81 gene acted as a strict Paternal Effect gene. Moreover, the biphasic pattern of developmental arrest was common to all the alleles. These findings strongly suggested that the unusual embryonic phenotype caused by all five new alleles was due to loss of function of the K81+ gene. The K81 gene is therefore the first clear example of a strict Paternal Effect gene in Drosophila. Based on the embryonic lethal phenotypes, we suggest that the K81+ gene encodes a sperm-specific product that is essential for the male pronucleus to participate in the first few embryonic nuclear divisions.
Jan Tesarik - One of the best experts on this subject based on the ideXlab platform.
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high magnification icsi overcomes Paternal Effect resistant to conventional icsi
Reproductive Biomedicine Online, 2006Co-Authors: A Hazout, Martine Dumonthassan, A M Junca, Paul Cohen Bacrie, Jan TesarikAbstract:Previous studies have shown that repeated intracytoplasmic sperm injection (ICSI) failures can be caused by a Paternal Effect. Other studies have suggested that ICSI results are compromised if morphologically abnormal spermatozoa are injected into oocytes. This study was undertaken to evaluate the usefulness of a high-magnification optical system to select spermatozoa to be used for ICSI (high-magnification ICSI) in couples with repeated conventional ICSI failures. Couples with two or more previous conventional ICSI failures underwent an additional conventional ICSI attempt, followed by a high-magnification ICSI attempt. The outcomes of the two sequential attempts were compared. In 72 of these patients, sperm DNA integrity was assessed. In the whole group of 125 couples with repeated ICSI failures, high-magnification ICSI improved clinical outcomes (pregnancy, implantation, delivery and birth rates) without affecting biological outcomes (fertilization and cleavage rates, embryo morphology). The improvement of clinical ICSI outcomes was evident both in patients with an elevated degree of sperm DNA fragmentation and in those with normal sperm DNA status. It is concluded that high-magnification ICSI improves clinical outcomes in couples with previous repeated conventional ICSI failures.
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Paternal Effects on cell division in the preimplantation embryo
Reproductive Biomedicine Online, 2005Co-Authors: Jan TesarikAbstract:Abstract Cell divisions in the human preimplantation embryo can be compromised by deficiencies in sperm nuclear genome or sperm-derived developmentally relevant cytoplasmic factors, oocyte activating substance and centriole. Sperm nuclear deficiencies are usually not detected before the 8-cell stage of embryo development, when a major expression of sperm-derived genes has begun. Sperm cytoplasmic deficiencies can be detected as early as the 1-cell zygote and then throughout the preimplantation development. The terms ‘late Paternal Effect' and ‘early Paternal Effect' have been suggested to denote these two pathological conditions. The late Paternal Effect is associated with an increased incidence of sperm DNA fragmentation. No association with sperm DNA damage has been found for the early Paternal Effect. The diagnosis of the late Paternal Effect is thus based on the examination of sperm DNA integrity, which should be performed in cases of repeated assisted reproduction failure even if morphologically normal embryos result from fertilization with the patient's spermatozoa. The only element leading to the diagnosis of the early Paternal Effect is poor zygote and embryo morphology and low cleavage speed. The absence of increased sperm DNA damage does not exclude the presence of this pathology. ICSI with testicular spermatozoa has recently been shown to be an efficient treatment for the late Paternal Effect. The use of oral antioxidant treatment in this indication has also given promising results.
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late but not early Paternal Effect on human embryo development is related to sperm dna fragmentation
Human Reproduction, 2004Co-Authors: Jan Tesarik, Ermanno Greco, Carmen MendozaAbstract:BACKGROUND: It is known that repeated failure of assisted reproduction treatment (ART) can be due to a Paternal Effect. This study was undertaken to analyse the possible relationship between ART failure and sperm DNA fragmentation. METHODS: Zygote morphology and the percentage of spermatozoa with fragmented DNA (assessed by TUNEL) were compared in two groups using donor oocytes for ICSI attempts. The experimental group consisted of 18 infertile couples who had each undergone three previous failed ART attempts. The control group included 18 randomly selected infertile couples undergoing their first ICSI attempt. Both groups used sibling oocytes from the same donors. RESULTS: In 10 couples of the experimental group, the adverse Paternal Effect was evident as early as the zygote stage. This early Paternal Effect was not associated with sperm DNA fragmentation. In eight couples of the experimental group, the adverse Paternal Effect did not produce any perceptible deterioration of zygote morphology. However, this late Paternal Effect was associated with an increased percentage of spermatozoa with fragmented DNA. CONCLUSIONS: Early Paternal Effect can compromise ART outcomes in the absence of increased sperm DNA fragmentation. Evaluation of sperm DNA integrity is useful to detect late Paternal Effect, which is not associated with morphological abnormalities at the zygote and early cleavage stages.
Denny Sakkas - One of the best experts on this subject based on the ideXlab platform.
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extent of nuclear dna damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization
Fertility and Sterility, 2004Co-Authors: Emre Seli, David K Gardner, W B Schoolcraft, Odette Moffatt, Denny SakkasAbstract:Abstract Objective To determine whether the extent of ongoing apoptotic cell death measured as the presence of DNA strand breaks in spermatozoa affects embryo development to the blastocyst stage in IVF. Design A prospective comparative study. Setting A university IVF clinic and a private IVF clinic. Patient(s) Men (n = 49) undergoing infertility treatment with IVF. Intervention(s) After density gradient centrifugation preparation, part of the sperm sample was used for infertility treatment, and the rest was fixed in paraformaldehyde. Strand breaks in DNA that are indicative of apoptosis were detected by the in situ DNA nick end labeling (TUNEL) technique. A total of 15,000 spermatozoa from each sample were evaluated for TUNEL reactivity by flow cytometry. Main outcome measure(s) Percentage of ejaculated spermatozoa with DNA strand breaks indicative of apoptosis, blastocyst development rate, and pregnancy rate. Result(s) Blastocyst development showed a significant negative correlation with percentage TUNEL positivity in spermatozoa. When 20% was used as a cutoff for TUNEL positivity in sperm samples, the percentage of blastocyst development was 50% higher in the Conclusion(s) The extent of nuclear DNA fragmentation in prepared ejaculated spermatozoa used in IVF negatively correlates with blastocyst development. A larger series of patients needs to be assessed to determine whether this Paternal Effect on blastocyst development may also affect pregnancy outcome.
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blastocyst development from supernumerary embryos after intracytoplasmic sperm injection a Paternal influence
Human Reproduction, 1998Co-Authors: Youssef Shoukir, Didier Chardonnens, Aldo Campana, Denny SakkasAbstract:The success of intracytoplasmic sperm injection (ICSI) warrants further study on the role of Paternal factors in early human embryogenesis. To investigate whether poor sperm parameters can influence embryo development, we examined the development of ICSI-fertilized embryos to the blastocyst stage. We present results of blastocyst development from supernumerary ICSI embryos after co-culture on monkey kidney epithelial cells. In addition, we compare the development of supernumerary embryos to the blastocyst stage after ICSI and in-vitro fertilization (IVF). Of 168 supernumerary ICSI embryos, 45 (26.8%) developed to blastocysts. Sperm concentration and morphology did not influence blastocyst development. In contrast, blastocysts arose from spermatozoa that had a significantly higher (P = 0.015) forward progressive motility compared with spermatozoa from those patients who failed to produce blastocysts (42.7% versus 28.2%, respectively). Overall the rate of embryo development to the blastocyst stage after ICSI was lower (26.8%) than that after IVF (47.3%). When the rate of blastocyst development was calculated for patients with three or more supernumerary embryos, it remained significantly higher for the IVF patients than for the ICSI patients (45.6% versus 30.0%). There was no significant difference in the mean cell number and quality of the supernumerary embryos between the IVF and ICSI patients. This study confirms previous reports that have postulated that abnormal spermatozoa may manifest a negative Paternal Effect on preimplantation embryo development.
Jon Heron - One of the best experts on this subject based on the ideXlab platform.
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simulations and directed acyclic graphs explained why assortative mating biases the prenatal negative control design
Journal of Clinical Epidemiology, 2020Co-Authors: Paul Madleydowd, Dheeraj Rai, Stanley Zammit, Jon HeronAbstract:Abstract Objective The negative control design can be used to provide evidence for whether a prenatal exposure–outcome association occurs by in utero mechanisms. Assortative mating has been suggested to influence results from negative control designs, although how and why has not yet been adequately explained. We aimed to explain why mutual adjustment of maternal and Paternal exposure in regression models can account for assortative mating. Study Design and Setting We used directed acyclic graphs to show how bias can occur when modeling maternal and Paternal Effects separately. We empirically tested our claims using a simulation study. We investigated how increasing assortative mating influences the bias of Effect estimates obtained from models that do and do not use a mutual adjustment strategy. Results In models without mutual adjustment, increasing assortative mating led to increased bias in Effect estimates. The maternal and Paternal Effect estimates were biased by each other, making the difference between them smaller than the true difference. Mutually adjusted models did not suffer from such bias. Conclusions Mutual adjustment for maternal and Paternal exposure prevents bias from assortative mating influencing the conclusions of a negative control design. We further discuss issues that mutual adjustment may not be able to resolve.
Stanley Zammit - One of the best experts on this subject based on the ideXlab platform.
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simulations and directed acyclic graphs explained why assortative mating biases the prenatal negative control design
Journal of Clinical Epidemiology, 2020Co-Authors: Paul Madleydowd, Dheeraj Rai, Stanley Zammit, Jon HeronAbstract:Abstract Objective The negative control design can be used to provide evidence for whether a prenatal exposure–outcome association occurs by in utero mechanisms. Assortative mating has been suggested to influence results from negative control designs, although how and why has not yet been adequately explained. We aimed to explain why mutual adjustment of maternal and Paternal exposure in regression models can account for assortative mating. Study Design and Setting We used directed acyclic graphs to show how bias can occur when modeling maternal and Paternal Effects separately. We empirically tested our claims using a simulation study. We investigated how increasing assortative mating influences the bias of Effect estimates obtained from models that do and do not use a mutual adjustment strategy. Results In models without mutual adjustment, increasing assortative mating led to increased bias in Effect estimates. The maternal and Paternal Effect estimates were biased by each other, making the difference between them smaller than the true difference. Mutually adjusted models did not suffer from such bias. Conclusions Mutual adjustment for maternal and Paternal exposure prevents bias from assortative mating influencing the conclusions of a negative control design. We further discuss issues that mutual adjustment may not be able to resolve.