# Development/Validation of Rete Testis Microcannulation for the Assessment of Novel Chemical Scaffolds That Penetrate the Blood Testis Barrier

> **NIH NIH R61** · UNIVERSITY OF MINNESOTA · 2022 · $409,139

## Abstract

PROJECT SUMMARY
The innermost compartments of the testes’ seminiferous tubules are shielded from the general circulation by
the molecular and cellular anatomy of Sertoli cells that form a highly effective blood-tissue barrier. The BTB
presents a hurdle to scientific efforts aimed at developing male-directed contraceptives or fertility-enhancing
therapeutics that target developing sperm cells uniquely locatedwithin the “adluminal” compartment of
seminiferous tubules. Additionally, the adluminal compartment of seminiferous tubules is an “immune
privileged site”, providing a safe harbor where pathogens escape both host immunity and anti-pathogenic
therapeutics. Thus, developing this specialized tool will provide unique resources needed for institutions to
improve the effectiveness of drugs targeting a broad spectrum of human health issues.
Our central hypothesis is based on the premise that novel methods for sampling tissues and fluids located
behind the BTB will be of great benefit to de-risk drug discovery programs focused on developing therapeutics
directed at viral diseases, cancer, parasites and contraception. Our long-term research goals are to expedite
the development of pharmaceuticals that will be effective against targets located within the adluminal
compartment of the testes. Our objective for the R61 phase of this project is to develop and validate
procedures by which we can sample and analyze fluid from the rat’s rete testis, behind its BTB. Sampling fluid
from behind the rat BTB will allow researchers to verify how effectively their test drugs are able to cross the
BTB and interact with targets located in the testes’ pharmacologically privileged sites. Furthermore, we will
identify and validate molecular reference standards that will be used to compare relative abilities of test
compounds to cross the BTB. Finally, we will determine the feasibility of adapting the rat procedure to a mouse
system. Our objective for the R33 phase of this project is to identify unique chemical structures and/or
scaffolds that will penetrate the BTB and to also establish and validate a robust sampling method in the mouse
since it is the predominant species used for efficacy models ranging from fertility/contraception, infectious
disease and cancer. Although similar in structure and function, rat and mouse BTB can differ significantly in a
host of factors such as transporter and macromolecule composition.

## Key facts

- **NIH application ID:** 10490286
- **Project number:** 5R61HD103065-02
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** F. Kent Hamra
- **Activity code:** R61 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $409,139
- **Award type:** 5
- **Project period:** 2021-09-17 → 2023-09-16

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10490286

## Citation

> US National Institutes of Health, RePORTER application 10490286, Development/Validation of Rete Testis Microcannulation for the Assessment of Novel Chemical Scaffolds That Penetrate the Blood Testis Barrier (5R61HD103065-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10490286. Licensed CC0.

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