# GENITALIA OUTGROWTH AND HYPOSPADIAS

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2021 · $343,125

## Abstract

Abstract
Genital malformation including hypospadias represents the second most common male birth defect after
cardiac defect. In the past 50 years, hypospadias incidence has doubled along with other male reproductive
problems. It is suspected that fetal exposure to endocrine disruptors may have contributed to this increase.
However, the etiology of hypospadias is still largely unclear. Both environmental and genetic factors are
involved. In fact, our understandings of genital development in general are still very limited. A complete
understanding of genetic pathways governing genital development and masculinization and how perturbations
of these pathways lead to genital malformations will have immense applications to improve global health. In the
past few years, we have performed comprehensive genetic analyses on genital tubercle (GT) development in
the mouse and established a conserved genetic pathway (Wnt/β-cateninSp8Fgf8) in regulating body
appendage outgrowth, including limbs and external genitalia. Genetic interactions between Wnt and Shh
pathways in regulating both genitalia outgrowth and masculinization have also been described. Together,
these studies laid the foundation for understanding posterior embryonic development as well as how
environmental factors can influence genitalia development and cause hypospadias. Based on these findings,
this proposal will continue to use mouse genetics including a series of conditional mutant mice to investigate a
novel genetic pathway regulating GT outgrowth. In Aim I, We will characterize several knockout mouse models
to build a genetic pathway regulating GT outgrowth and patterning. In Aim II, we will use a novel and highly
innovative Split DamID technique to identify in vivo downstream targets of androgen receptor and β-catenin
during genital masculinization. Together, these studies should greatly improve our understanding of genitalia
development and hypospadias formation. Our long term goal is to use mouse molecular genetics to
understand the process of genital development and masculinization and the etiology of genital malformations,
such as hypospadias.

## Key facts

- **NIH application ID:** 10114273
- **Project number:** 5R01DK113642-05
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Liang Ma
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $343,125
- **Award type:** 5
- **Project period:** 2017-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10114273

## Citation

> US National Institutes of Health, RePORTER application 10114273, GENITALIA OUTGROWTH AND HYPOSPADIAS (5R01DK113642-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10114273. Licensed CC0.

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