Takafumi Utsunomiya

Tohoku University, Sendai-shi, Miyagi-ken, Japan

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Publications (30)70.65 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: DNA methylation is globally reprogrammed during mammalian preimplantation development, which is critical for normal development. Recent reduced representation bisulfite sequencing (RRBS) studies suggest that the methylome dynamics are essentially conserved between human and mouse early embryos. RRBS is known to cover 5-10% of all genomic CpGs, favoring those contained within CpG-rich regions. To obtain an unbiased and more complete representation of the methylome during early human development, we performed whole genome bisulfite sequencing of human gametes and blastocysts that covered>70% of all genomic CpGs. We found that the maternal genome was demethylated to a much lesser extent in human blastocysts than in mouse blastocysts, which could contribute to an increased number of imprinted differentially methylated regions in the human genome. Global demethylation of the paternal genome was confirmed, but SINE-VNTR-Alu elements and some other tandem repeat-containing regions were found to be specifically protected from this global demethylation. Furthermore, centromeric satellite repeats were hypermethylated in human oocytes but not in mouse oocytes, which might be explained by differential expression of de novo DNA methyltransferases. These data highlight both conserved and species-specific regulation of DNA methylation during early mammalian development. Our work provides further information critical for understanding the epigenetic processes underlying differentiation and pluripotency during early human development.
    PLoS Genetics 12/2014; 10(12):e1004868. · 8.52 Impact Factor
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    ABSTRACT: To assess the clinical value of bisulfite polymerase chain reaction Luminex (BPL), an automated, high-throughput procedure for the detection of alterations in DNA methylation. Experimental prospective study. University research laboratory and private in vitro fertilization (IVF) clinic. A total of 337 men, 61 with severe oligozoospermia, 67 with moderate oligozoospermia, and 209 with microscopically normozoospermia. The ejaculated sperm samples after the routine semen analysis with patients' consent. Examination of the methylation patterns of eight imprinted loci in sperm DNA, and confirmation with combined bisulfite PCR restriction analysis (COBRA). A total of 47 cases (13.9%) showed abnormal methylation at one or more imprinted loci (18 paternal, 18 maternal, and 11 cases with alterations of both maternal and paternal imprints). The relative ease of the BPL method provides a practical method within a clinical setting to reduce the likelihood of abnormal samples being used in assisted reproduction treatments.
    Fertility and sterility 01/2011; 95(1):129-34, 134.e1-4. · 3.97 Impact Factor
  • Fertility and Sterility - FERT STERIL. 01/2010; 94(4).
  • Fertility and Sterility 09/2009; 92(3). · 4.17 Impact Factor
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    ABSTRACT: There is an increased prevalence of imprinting disorders, such as Beckwith-Wiedemann syndrome, associated with human assisted reproductive technologies (ART). Work on animal models suggests that in vitro culture may be the source of these imprinting errors. However, in this study we report that, in some cases, the errors are inherited from the father. We analyzed DNA methylation at seven autosomal imprinted loci and the XIST locus in 78 paired DNA samples. In seven out of seventeen cases where there was abnormal DNA methylation in the ART sample (41%), the identical alterations were present in the parental sperm. Furthermore, we also identified DNA sequence variations in the gene encoding DNMT3L, which were associated with the abnormal paternal DNA methylation. Both the imprinting errors and the DNA sequence variants were more prevalent in patients with oligospermia. Our data suggest that the increase in the incidence of imprinting disorders in individuals born by ART may be due, in some cases, to the use of sperm with intrinsic imprinting mutations.
    European journal of human genetics: EJHG 06/2009; 17(12):1582-91. · 3.56 Impact Factor
  • Eiko Otsu, Akiko Sato, Kyoko Kido, Takafumi Utsunomiya
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    ABSTRACT: No abstract available.
    Journal of Mammalian Ova Research 01/2009;
  • Akiko Sato, Eiko Otsu, Takahiro Arima, Takafumi Utsunomiya
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    ABSTRACT: No abstract available.
    Journal of Mammalian Ova Research 01/2009;
  • T. Shinoda, M. Sashiyama, K. Ueno, T. Utsunomiya
    Fertility and Sterility - FERT STERIL. 01/2009; 92(3).
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    ABSTRACT: PurposeSeveral recent reports have discussed refrozen and thawed embryo transfer; however, the process may cause a degree of chromosomal damage and subtle genomic mutation. In view of this possibility, the purpose of this study was to investigate the incidence of aneuploidy in refrozen embryos. MethodsIn order to investigate the incidence of aneuploidy and mosaicism observed in chromosome 1, fluorescent in situ hybridization (FISH) was used on surviving embryos that first underwent one freeze-thaw cycle, then were allowed to develop to the blastocyst stage, and subsequently survived a second freeze-thaw cycle. ResultsOf 1,132 blastomeric nuclei analyzed from 15 refrozen embryos, disomy was found in 82.9%. In contrast, for the 11 blastocysts subjected to only one freeze-thaw cycle, disomy was noted in 78.4%. Of the 197 blastomeric nuclei analyzed in all arrested embryos, disomy was found in 51.8%. ConclusionsThe refreezing process did not increase aneuploidy. The good and fair morphology groups demonstrated a higher percentage of disomy than the poor morphology group regardless of whether they were frozen once or twice.
    Reproductive Medicine and Biology 01/2009; 8(3):103-106.
  • Fertility and Sterility 09/2008; 90:S37. · 4.17 Impact Factor
  • Yoko Kumasako, Eiko Otsu, Takafumi Utsunomiya, Yasuhisa Araki
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    ABSTRACT: To confirm the clinical benefits of recryopreserved, twice-thawed embryo transfer (ET). Retrospective study. Private fertility clinic. Forty-nine women whose embryos had been refrozen after a previous frozen-thawed ET. None. Comparison of implantation and pregnancy rates of twice-cryopreserved, twice-thawed embryos versus once-cryopreserved, once-thawed embryos. The pregnancy rate per ET cycle was 27.8% in the refrozen group and 25.9% in the control group (no statistically significant difference). The implantation rate was 25.0% in the refrozen group and 19.3% in the control group (no statistically significant difference). The refreezing of supernumerary embryos can prevent ovarian hyperstimulation syndrome in stimulated patients and in those who have experienced repeated failed pregnancies. If unexpected supernumerary embryos are available for recryopreservation after frozen-thawed ET, these embryos may be revitrified for a future transfer.
    Fertility and sterility 03/2008; 91(2):383-6. · 3.97 Impact Factor
  • Journal of Mammalian Ova Research 01/2008; 25(1):2-7.
  • Fertility and Sterility - FERT STERIL. 01/2008; 90.
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    ABSTRACT: Recent studies suggest that assisted reproductive technologies (ART), which involve the isolation, handling and culture of gametes and early embryos, are associated with an increased incidence of rare imprinting disorders. Major epigenetic events take place during this time and the process of ART may expose the epigenome to external influences, preventing the proper establishment and maintenance of genomic imprints. However, the risks of ART cannot be simply evaluated because the patients who receive ART may differ both demographically and genetically from the general population at reproductive age. In this study, we examined the DNA methylation status of seven imprinted genes using a combined bisulphite-PCR restriction analysis and sequencing technique on sperm DNA obtained from 97 infertile men. We found an abnormal paternal methylation imprint in 14 patients (14.4%) and abnormal maternal imprint in 20 patients (20.6%). The majority of these doubly defective samples were in men with moderate or severe oligospermia. These abnormalities were specific to imprinted loci as we found that global DNA methylation was normal in these samples. The outcome of ART with sperm shown to have an abnormal DNA methylation pattern was generally poor. However, one sample of sperm with both paternal and maternal methylation errors used in ICSI produced a child of normal appearance without any abnormalities in their imprinted methylation pattern. Our data suggest that sperm from infertile patients, especially those with oligospermia, may carry a higher risk of transmitting incorrect primary imprints to their offspring, highlighting the need for more research into ART.
    Human Molecular Genetics 12/2007; 16(21):2542-51. · 7.69 Impact Factor
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    ABSTRACT: The predictive value of the morphology of the cumulus--oocyte complex (COC) has not yet been explored as a possible factor contributing to the success of human in-vitro maturation (IVM). In the present study, development-supporting competency of oocytes encircled in a large ( > or = 5) (grade A), moderate (3 approximately 4) (grade B) or small ( < or = 2) (grade C) number of cumulus cell layers was assessed, together with changes in hormonal profile following a truncated course of 150 IU pure FSH administration for 3 days prior to aspiration on laparoscopy indicated for endometriosis. FSH priming increased the number of COC aspirated without changing the proportion of the three morphological types of COC, which were then subjected to IVM in the presence of 200 mIU/ml FSH plus 1000 mIU/ml human chorionic gonadotrophin, followed by intracytoplasmic sperm injection. The highest development-supporting competence was observed not with oocytes in grade A COC harvested from natural cycles, but with oocytes in grade B COC from FSH-primed cycles. Hormonal profiles in patients bearing grade B COC were characterized by moderate response in oestradiol and progesterone production following FSH, with LH/FSH ratio being below 1.0. It is concluded that an optimal window of hormonal profile(s) may exist for follicle aspiration to obtain grade B COC in FSH-stimulated human IVM cycles.
    Reproductive biomedicine online 02/2007; 14(1):49-56. · 2.68 Impact Factor
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    A Sato, E Otsu, H Negishi, T Utsunomiya, T Arima
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    ABSTRACT: There is an increased incidence of rare imprinting disorders associated with assisted reproduction technologies (ARTs). The sex-specific epigenetic modifications that are imposed during gametogenesis act as a primary imprint to distinguish maternal and paternal alleles. The most likely candidate for the gametic mark is DNA methylation. However, the timing of DNA methylation acquisition in adult oocytogenesis and the effects of superovulation are unknown. We examined the maternal methylation of PEG1(MEST), LIT1(KCNQ1OT1) and ZAC(PLAGL1) and the paternal methylation of H19 in adult growing oocytes of humans and mice and compared them with the methylation status of mouse neonatal growing oocytes by using bisulphite sequencing. Furthermore, we examined the effects of superovulation in the human and mouse. Maternal methylation of these genes has already been initiated to some extent in adult human and mouse non-growing oocytes but not in mouse neonates. In addition, the methylation dynamics during adult human and mouse oocyte development changed more gradually than those during neonatal oocyte development. Furthermore, we found the demethylation of PEG1 in growing oocytes from some ART-treated infertile women and a gain in the methylation of H19. We also detected methylation changes in superovulated mice. Our studies in the human and mouse suggest that superovulation can lead to the production of oocytes without their correct primary imprint and highlight the need for more research into ARTs.
    Human Reproduction 02/2007; 22(1):26-35. · 4.67 Impact Factor
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    ABSTRACT: Asynchrony between embryo development and endometrial differentiation is the limiting step of successful pregnancy in assisted reproduction. The aim of this study was to investigate whether or not post-thaw synchronization culture of day 5-6 frozen embryos, prior to transfer, with endometrial differentiation resulted in pregnancy. A total of 142 cycles of 134 patients were transferred in three protocols. Blastocysts with cavities larger than half of the entire blastocyst volume were transferred without synchronizing culture on day 5 or 6 of progesterone commencement (P5/6) in hormone replacement treatment cycles (protocol 1). Blastocysts with cavitation below half of the entire blastocyst were cultured for 1 or 2 days after thawing prior to transfer on P5 or P6 (protocol 2). Morulae and very early stage blastocysts were thawed on the days corresponding to P5 and P6, and only the embryos that reached expanded or hatching blastocysts were transferred on P7 without synchronizing culture (protocol 3). Pregnancy rate in protocol 2 (32.0%) was comparable with that of protocol 1 (35.0%). It is concluded that developmentally retarded frozen embryos can be rescued with synchronizing culture prior to transfer by evading asynchrony.
    Reproductive biomedicine online 06/2006; 12(5):622-9. · 2.68 Impact Factor
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    Yoko Kumasako, Mami Kumon, Takafumi Utsunomiya, Yasuhisa Araki
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    ABSTRACT: To report on successful birth after the transfer of postthawed human zygotes that were vitrified using a conventional straw for the purpose of protecting them from infections and a low-toxicity cryoprotectant that is commercially sold. A primary infertile couple presented at our IVF program. After being checked for fertilization, the embryos were not transferred to the uterus at that cycle. Instead, all of them were cryopreserved at the 2-pronuclei stage using our original vitrification method. After the vitrification and warming of four zygotes, two embryos were transferred into the uterus. Twenty-one 2-pronuclei embryos were vitrified in liquid nitrogen. After 2 embryos were thawed and transferred, successful pregnancy was the outcome, and a healthy boy was born at term. Vitrification is a simple procedure and requires less time than slow freezing. Vitrification of zygotes in a conventional straw seems to be sufficient for viability and works to store the zygotes safely.
    Journal of Assisted Reproduction and Genetics 02/2005; 22(1):33-5. · 1.82 Impact Factor
  • Fertility and Sterility - FERT STERIL. 01/2005; 84.
  • Fertility and Sterility - FERT STERIL. 01/2005; 84.

Publication Stats

564 Citations
70.65 Total Impact Points


  • 2009–2011
    • Tohoku University
      • Graduate School of Medicine
      Sendai-shi, Miyagi-ken, Japan
  • 2008
    • Yamagata University
      Ямагата, Yamagata, Japan
  • 2003–2004
    • Oita University
      Ōita, Ōita, Japan
    • St. Luke's International Hospital
      Edo, Tōkyō, Japan