Institute for Biogenesis Research
University of Hawaii John A. Burns School of Medicine

Supported by IBR-COBRE (Center of Biomedical Research Excellence) IDeA Program
NCRR 5P20RR024206-01, NIGMS 8P20GM103457-05

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Name Yukiko Yamazaki
Affiliation JABSOM
Position Associate Professor
Degree Ph.D. (Kitasato University, Japan)
Phone 808-692-1416
Fax 808-692-1962
Address 651 Ilalo St., BSB 163-3
Honolulu, HI96813

Research projects:

Mechanisms of Sex Differentiation in Fetal Germ Cells.
Effects of Assisted Reproductive Technologies (ART) in Mammalian Development.

Description of research:

My primary research interest is the mechanisms of sex differentiation in fetal germ cells. In mammals, primordial germ cells (PGCs) are the precursors of sperm and oocytes. The sex-specific development of PGCs as sperm or oocytes is initiated by cues provided by the gonadal environment. After an initial sex differentiation event in the gonads, PGCs in a female gonad immediately enter meiosis, thereby committing oogenesis. On the other hand, PGCs in a male gonad do not enter meiosis until puberty. Instead, they first enter mitotic arrest and maintain G0 stage until after birth. Recent findings reveal that the sex-specific timing of meiosis entry is regulated by retinoic acid (RA) and RA degenerating enzyme in the gonads. Our goal is to elucidate how the molecular environment regulates the sex differentiation of fetal germ cells. Using a germ-cell culture system, we have examined mechanisms of entry into meiosis or mitotic arrest in the fetal germ cells. Besides meiosis, another unique event of the germ cells after sex differentiation is epigenetic reprogramming of genomic imprinting. Our group has examined how this epigenetic reprogramming of genomic imprinting is regulated to establish sex-specific imprints in the germ cells.

I am also interested in the effects of Assisted Reproductive Technologies (ART) in mammalian development. In human being, the majority of children conceived through ART, such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI), appear healthy; however, metabolic abnormalities have been reported. As an animal model, we have studied the effects of these techniques on obesity and the epigenetic status of imprinted and non-imprinted genes in mouse offspring (collaborations).

Selected Publications:

  • Yamazaki Y, Wakayama T, Yanagimachi R. Contribution of cumulus cells and serum for the maturation of oocyte cytoplasm as revealed by intracytoplasmic sperm injection (ICSI). Zygote 2001; 9: 277-282.
  • Yamazaki Y, Makino H, Hamaguchi- Hamada K, Hamada S, Sugino H, Kawase E, Miyata T, Ogawa M, Yanagimachi R, Yagi T. Assessment of the developmental totipotency of neural cells in the cerebral cortex of mouse embryo by nuclear transfer. Proc. Natl. Acad. Sci. USA 2001; 98: 14022-14026.
  • Tamashiro KLK, Wakayama T, Akutsu H, Yamazaki Y, Lachey J, Wortman MD, Seeley RJ, D’Alessio, DA, Woods SC, Yanagimachi R, Sakai R. Nature Med. 2002; 8: 262-267.
  • Marh J, Tres LL, Yamazaki Y, Yanagimachi R, Kierszenbaum AL. Spermatids developed in vitro from pre-existing spermatocytes can produce normal offspring by nuclear transfer. Biol. Reprod. 2003; 69: 169-76.
  • Yamazaki Y, Mann MRW, Lee SS, Marh J, McCarrey JR, Yanagimachi R, Bartolomei MS. Reprogramming of primordial germ cells begins before their migration into the genital ridge making primordial germ cells inadequate nuclear donors for reproductive cloning. Proc. Natl. Acad. Sci. USA 2003; 100: 12207- 12212.
  • Ohgane J, Wakayama T, Senda S, Yamazaki Y, Inoue K, Ogura A, Marh J, Tanaka S, Yanagimachi R, Shiota K. The sall3 locus is an epigenetic hotspot of aberrant DNA methylation associated with placentomegaly of cloned mice. Genes to Cells 2004; 9: 253-260. Senda S, Wakayama T, Yamazaki Y, Ohgane J, Hattori N, Tanaka S, Yanagimachi R, Shiota K. Skewed X-inactivation in cloned mice. Biochem Biophy Res Comm (BBRC) 2004; 321, 38-44.
  • Makino, H. Yamazaki Y, Hirabayashi T, Kaneko R, Hamada S, Osada T, Kawamura Y, Yanagimachi R, Yagi T. Mouse embryos and chimera cloned from neural cells in the postnatal cerebral cortex. Cloning and Stem Cells. 2005; 7: 45-61.
  • Yamazaki Y, Low EW, Marikawa Y, Iwahashi K, Bartolomei MS, McCarrey JR, Yanagimachi R. Adult mice cloned from migrating primordial germ cells. Proc. Natl. Acad. Sci. USA 2005; 102, 11361-11366.
  • Osada T, Tamamaki N, Song S-Y, Kakazu N, Yamazaki Y, Makino H, Sasaki A, Hirayama T, Hamada S, Nave K-A, Yanagimachi R, Yagi T. Mice cloned from differentiated neurons of the cerebral cortex of juvenile mice by nuclear transfer and tetrapomplementation of neuron-derived ES cells. J. Neurosci. 2005; 25, 8368-8374.
  • Yamazaki Y, Fujita TC, Low EW, Alarcon VB, Yanagimachi R, Marikawa Y. Gradual DNA demethylation of the Oct4 promoter in cloned mouse embryos. Mol. Reprod. Dev.2006; 73, 180-186.
  • Coussens M, Yamazaki Y, Moisyadi S, Suganuma R, Yanagimachi R, Allsopp R. Regulation and effects of modulation of telomerase reverse transcriptase expression in primordial germ cells during development. Biology of Reproduction 2006; 75: 785-791.
  • Tamashiro KL, Sakai RR, Yamazaki Y, Wakayama T, Yanagimachi R. Developmental, behavioral, and physiological phenotype of cloned mice. Adv. Exp. Med. Biol. 2007; 591, 72-83.
  • Caperton L, Murphey P, Yamazaki Y, McMahan CA, Walter CA, Yanagimachi R, McCarrey JR. Assisted reproductive technologies do not alter mutation frequency or spectrum. Proc. Natl. Acad. Sci. USA 2007; 104, 5085-5090.
  • Senda S, Wakayama T, Arai Y, Yamazaki Y, Ohgane J, Tanaka S, Hattori N, Yanagimachi R, Shiota K. DNA methylation errors in cloned mice disappear with advancement of aging. Cloning and Stem Cells. 2007; 9: 293-302.
  • Iwahashi K, Yoshioka H, Low EW, McCarrey JR, Yanagimachi R, Yamazaki Y. Autonomous regulation of sex-specific developmental programming in mouse fetal germ cells. Biology of Reproduction 2007; 77, 697-706.
  • Yoshioka H, McCarrey JR, Yamazaki Y. Dynamic nuclear organization of constitutive heterochromatin during fetal male germ cell development in mice. Biology of Reproduction 2009; 80, 804-812.
  • Murphey P, Yamazaki Y, McMahan CA, Walter AC, Yanagimachi R, McCarrey JR. Epigenetic regulation of genetic integrity is reprogrammed during cloning. Proc. Natl. Acad. Sci. USA 2009; 106, 4731-4735.
  • Oda M, Tanaka S, Yamazaki Y, Ohta H, Iwatani M, Suzuki M, Ohgane J, Hattori N, Yanagimachi R, Wakayama T, Shiota K. Establishment of trophoblast stem cell lines from somatic cell nuclear-transferred embryos. Proc. Natl. Acad. Sci. USA 2009; 106: 16293-16297.
  • Scott KA, Yamazaki Y, Yamamoto M, Lin Y, Melhorn SJ, Krause EG, Woods SC, Yanagimachi R, Sakai RR, Tamashiro KLK. Glucose parameters are altered in mouse offspring produced by assisted reproductive technologies and somatic cell nuclear transfer. Biology of Reproduction 2010; 83, 220-227.
  • Ohta K, Lin Y, Hogg N, Yamamoto M, Yamazaki Y. Direct effects of retinoic acid on entry of fetal male germ cells into meiosis in mice. Biology of Reproduction 2010 (in press)

Lab members

Carolyn Higuchi
Graduate Student (DRB program)
LAB Phone: 692-1750
Ferhat Ulu
Graduate Student (DRB program)
LAB Phone: 692-1750