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Your Environment. Your Health.

Reproductive Developmental Biology Group

Organogenesis of Reproductive Organs

Humphrey Hung-Chang Yao, Ph.D.
Humphrey Yao, Ph.D.
Senior Principal Investigator
Tel 984-287-4004
humphrey.yao@nih.gov
P.O. Box 12233
Mail Drop C4-10
Durham, N.C. 27709

Research Summary

Humphrey Yao, Ph.D., leads the Reproductive Developmental Biology Group, and holds a secondary appointment in the NIEHS Epigenetics & Stem Cell Biology Laboratory. The main thrust of the 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 disorders of sex development. 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 and reproductive tracts as a model to understand the basic process of organ formation and the potential implication of the impacts of endocrine disruptor exposure to reproductive organ formation in fetuses and fertility in adulthood. Reproductive organs 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.

This image depicts the different cell types (Sertoli cells and Steroidogenic Leydig cells) and morphological characteristics (testis cords) in the developing mouse testis at embryonic day 15.5.
A micrograph of fetal testicular cells.

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 formed in the fetal testis and ovary, respectively.
  • Defining the cellular processes that lead to sexually dimorphic establishment of the reproductive tracts.
  • Investigating the effects of in utero exposure to endocrine disruptors on organogenesis of reproductive organs and lingering impacts on fertility in adulthood.

Current Projects:

  • Define the linage progression roadmap of somatic cells in the gonads by single cell sequencing (Drop-seq and combinatorial indexing technique).
  • Identify novel players in gonadal organogenesis using conditional genetic approaches, ChIP-seq, ATAC-seq, and RNA-seq.
  • Investigate the molecular interaction between COUP-TFII, androgen receptors, and other transcription factors in maintaining the male reproductive tract.
  • Examine the impact of in utero exposure to endocrine disrupting agents (arsenic and phthalates) on reproductive organ development and fertility.

Yao received his doctoral degree at the University of Illinois in Urbana-Champaign in 1999 and then 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 moved to NIEHS in 2010 and was promoted to Senior Investigator in 2018.

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