# Circumventing the Blood-Testis Barrier

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $295,488

## Abstract

PROJECT SUMMARY
The testis and epididymis mark the initial portion of the male genital tract (MGT) and are
impermeable to most hydrophilic compounds due to tight junctions. This barrier ─ the blood-
testes barrier (BTB) ─ can act as an obstacle for therapies requiring entry into these tissues for
full effect; for example contributing to testicular relapse in acute lymphoblastic leukemia (ALL)
or acting as a sanctuary site for HIV infection. However, these epithelial barriers are known to
express alternative xenobiotic transporters that may be utilized to allow select agents to gain
access to the MGT and reduce the frequency of testicular relapse or HIV transmission. Rather
than studying why drugs fail to cross the BTB, the major focus of our studies is to characterize the
endogenous transport processes that could allow drugs to access the MGT. We hypothesize that
the penetration of MGT relevant drugs into the BTB occurs through transport processes that can
be modeled computationally, and that therapeutic concentration of these drugs is greatly affected
by epididymal transporters and water reabsorption. Our grant focuses on 3 aims: Aim 1: Establish
the transepithelial transport mechanisms by which MGT relevant drugs can cross the BTB and
develop a predictive model for rational therapeutic design. Aim 2: Determine the impact of
epididymal water reabsorption on drug concentrations within the MGT in vivo. Aim 3: Determine
whether nucleoside transport is supported in the epididymis and the impact on nucleoside-based
drug disposition. Understanding these pathways will be foundational for the development of
drugs, such as antiviral, chemotherapy, contraception, and fertility agents, that require access to
the MGT in order to achieve full therapeutic effect.

## Key facts

- **NIH application ID:** 9836855
- **Project number:** 5R01GM123643-04
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** Nathan J Cherrington
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $295,488
- **Award type:** 5
- **Project period:** 2017-04-01 → 2021-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9836855

## Citation

> US National Institutes of Health, RePORTER application 9836855, Circumventing the Blood-Testis Barrier (5R01GM123643-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9836855. Licensed CC0.

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