# Molecular Mechanisms of Leydig Cell Regeneration

> **NIH NIH F31** · JOHNS HOPKINS UNIVERSITY · 2021 · $46,036

## Abstract

Cells lost to normal wear and tear in many adult tissues are replaced with the activity of stem cells. In response
to injury, however, cells can use entirely different strategies to repair and regenerate tissues. Injured tissues
can be regenerated through the activation of stem cells or from progenitor cells that, unlike stem cells, are
incapable of asymmetric division and self-renewal. The dramatic cellular changes that occur during
regeneration are thought to arise from altered signaling in the tissue microenvironment, or niche, but the
mechanisms regulating regeneration are largely unknown. A classical model of regeneration after injury is the
adult rat testis. In the testis, somatic cells create a microenvironment that contributes to the germ cell niche.
Critical somatic support cells include Leydig cells, the major androgen producing cells in males, which are
required for male health and fertility. Although Leydig cells are a quiescent cell type, and not thought to divide
under normal conditions, they are chemically ablated by ethane dimethane sulfonate (EDS). Several weeks
after chemical ablation, new Leydig cells repopulate the testis. The mechanism of Leydig cell regeneration and
the progenitors from which they arise remain poorly understood, partially due to the lack of genetic tools
available in rats. In vitro work has hinted at candidate markers that may identify progenitors of Leydig cell
regeneration. The goal of this project is to determine the cellular mechanism and molecular mechanism of
Leydig cell regeneration. Mouse genetics make it possible to interrogate the cellular mechanism of
regeneration by use of an inducible genetic lineage tracing system. In preliminary data, a subset of somatic
testis interstitial cells trace into new Leydig cells after ablation in mice. We will continue using this model to
determine the both identity of the progenitor cells and whether this cell type is self-renewing. We will also
determine the molecular mechanisms driving regeneration with the use of sc-RNA sequencing before, during,
and after regeneration. Candidate genes implicated in signaling and Leydig cell development that are
differentially expressed in regenerating cells will be tested for functional roles during regeneration using small
molecule pathway inhibitors and available genetic tools. While small molecules are an accessible way to gain
crude information about whether a signaling pathway is involved, sc-RNA sequencing will illuminate exactly
which cells produce signals that initiate the progenitor response. Determining the cellular and molecular
mechanisms of Leydig cell regeneration will significantly contribute to the understanding of adult tissue
regeneration in vivo with broader implications for male fertility and health.

## Key facts

- **NIH application ID:** 10233377
- **Project number:** 1F31HD105407-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Jasmin LaKia Jeffery
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $46,036
- **Award type:** 1
- **Project period:** 2021-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10233377

## Citation

> US National Institutes of Health, RePORTER application 10233377, Molecular Mechanisms of Leydig Cell Regeneration (1F31HD105407-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10233377. Licensed CC0.

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