# Role of the extracellular matrix during Wolffian/epididymal duct morphogenesis

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2020 · $335,113

## Abstract

PROJECT SUMMARY
The epididymis provides a unique luminal fluid microenvironment that allows for sperm maturation and survival,
and disruptions to this function lead to male infertility. Further, disruptions to epididymal function may also arise
as a consequence of abnormal fetal development, although very little is known either of the process of Wolffian
duct/epididymal development or of the nature and causes of congenital defects that lead to male infertility. The
central hypothesis of this application is that elongation and coiling of the Wolffian duct is crucial for
the function of the resulting epididymis, and that failure to elongate and coil leads to male infertility.
The overall goal is two-fold, to examine: (a) the mechanisms by which cells move to elongate the duct and (b)
to dissect the underlying cellular and molecular mechanisms that regulate those cell movements. Although we
have evidence that epithelial cells move by intercalating, we will test the hypothesis that intercalation-type
movements of the mesenchyme cells that surround the duct and the en masse movement of mesenchymal
cells in the interstitium contribute to ductal elongation and coiling. A combination of genetically modified mice,
advanced microscopy including confocal, second harmonic two-photon, and atomic force microscopy, in vitro
organ culture and contemporary software analyses will be used to test the hypotheses outlined in the following
three specific aims: (1) To test the hypothesis that the stiffness (modulus) of the ECM undergoes dynamic
changes during Wolffian duct morphogenesis thereby providing a biomechanical environment that promotes
epithelial and mesenchymal cell intercalation and en masse movement of mesenchymal cells within the
interstitium. (2) To test the hypothesis that radial intercalation of mesenchymal cells and the en mass
movements of mesenchymal cells within the interstitium are major drivers of Wolffian duct elongation and
coiling. (3) To test the hypothesis that Ptk7 and Rac1 regulate radial intercalation and en masse movement of
mesenchymal cells via regulating ECM biomechanical properties through changes in its deposition and
assembly during Wolffian duct development, which in turn are important for male fertility. Therefore, this
application focuses on the role of the ECM during Wolffian duct morphogenesis paying special attention to the
importance of its assembly, distribution and stiffness, and how this is coordinated to regulate mediolateral and
radial intercalation of epithelial and mesenchymal cells respectively, and the en masse movement of
mesenchymal cells within the interstitium. Coordination of these events is critical for Wolffian/epididymal duct
development, and therefore, male fertility. The anticipated outcomes of this study will not only have a major
impact on an area of reproductive biology that has been poorly understood, but will also contribute to our
understanding of the fundamental process of tubular morphogenesis. Spe...

## Key facts

- **NIH application ID:** 9980704
- **Project number:** 5R01HD093703-03
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Barry T. Hinton
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $335,113
- **Award type:** 5
- **Project period:** 2018-08-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980704

## Citation

> US National Institutes of Health, RePORTER application 9980704, Role of the extracellular matrix during Wolffian/epididymal duct morphogenesis (5R01HD093703-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980704. Licensed CC0.

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