Reproductive Developmental Biology Group
Organogenesis of Reproductive Organs
Humphrey Hung-Chang Yao, Ph.D.
The main thrust of the Reproductive Developmental Biology Group is to define the normal process of how gonads and reproductive tracts form during embryogenesis and investigate whether this process is susceptible to in utero exposure to endocrine disruptors.
Compelling animal evidence and human epidemiological data have revealed that impairment of fetal organ development has profound consequences on adult health. The concept of "fetal origins of adult diseases" also applies to the reproductive systems where formation of most reproductive organs is completed before birth. Defects in reproductive organ formation manifest as birth defects in severe cases, i.e., pseudohermaphroditism. However, minor abnormalities are often left undetected and become a potential cause of fertility problems and neoplasia when the affected individual reaches adulthood.
The Reproductive Developmental Biology Group uses organogenesis of the gonads as a model to understand the basic process of organ formation and the potential implication of the impacts of endocrine disruptor exposure to gonad development in fetuses and fertility in adulthood. Gonads are one of the few organs that exhibit dramatic sex-specific pattern of dimorphic development. This unique pattern of development provides a model to understand not only the mechanism of sex determination, but also how progenitor cells make the decision to differentiate into tissue-specific cell types, the fundamental concept of embryology.
Testes and ovaries are derived from a common gonadal primordium, which is morphologically indistinguishable in either sex before the onset of sex determination. The gonadal primordium undergoes dramatic changes at the onset of sex determination, 11.5 days and 6 weeks of pregnancy in mouse and human, respectively. The presence or absence of the Y chromosome determines the sex of the gonads in most mammals. In the XY embryo, the Y-linked SRY gene (Sex-determining Region of the Y chromosome) triggers a cascade of events that direct the gonadal primordium to differentiate into a testis. However, in the XX embryo where the Sry gene is absent, the gonadal primordium becomes an ovary. The group's main focus is to understand the molecular and cellular mechanisms underlying the formation of testis and ovary.
Major areas of research:
- Understanding how different somatic cell lineages — Sertoli and Leydig cells in the testis and granulose and theca cells in the ovary — are established in the fetal testis and ovary, respectively.
- Defining the cellular processes that lead to the formation of testis architecture and follicle assembly in the ovary.
- Investigating the effects of in utero exposure to endocrine disruptors on gonad organogenesis and lingering impacts on fertility in adulthood.
- Exploring the potential extra-gonadal origin of fetal Leydig cells in the testis and theca cells in the ovary and the involvement of the Hedgehog pathway in this process.
- Identifying novel players in the Wnt4/beta-catenin pathway in ovary organogenesis using conditional genetic approaches, ChIP-seq, and microarray.
- Investigating the molecular mechanism in which in utero exposure to BPA induces testicular dysgenesis and follicular atresia and its impact on fertility when exposed animals reach adulthood.
- Establishing chick embryos as a comparative model to study the molecular mechanism of gonad organogenesis and environmental exposure.
Humphrey Yao, Ph.D., leads the Developmental Reproductive Biology Group within the Laboratory of Reproductive and Developmental Toxicology. Yao received his doctoral degree from the University of Illinois in Urbana-Champaign in 1999 and completed his postdoctoral training at Duke University Medical Center in 2002. He became assistant professor in the Department of Comparative Biosciences at University of Illinois in Urbana-Champaign in 2003 and received tenure in 2009. Yao joined NIEHS in August 2010.