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).