# Next Generation Therapies for Fertility Preservation in Male Cancer Patients

> **NIH NIH R01** · MAGEE-WOMEN'S RES INST AND FOUNDATION · 2021 · $791,664

## Abstract

Summary
Medical treatments for cancer or other non-malignant conditions can cause permanent infertility. The only
fertility preservation option available to prepubertal male patients who are not producing sperm is experimental
testicular tissue freezing. Prepubertal boys do have spermatogonial stem cells (SSCs) in their testes that have
the potential to produce sperm. With this in mind, academic centers around the world are cryopreserving
testicular tissues for boys in anticipation that those tissues can be used in the future to restore fertility.
Although methods to produce sperm and live offspring from immature frozen tissues have been developed in
mice, translation to efficient and safe methods to produce sperm from those tissues in humans has not been
achieved. We will use our rhesus macaque model of cancer survivorship to test next generation technologies
that might be used to protect endogenous SSCs from gonadotoxic therapies or produce sperm and offspring
from cryopreserved, prepubertal testicular tissues. In addition, each patient who preserves testicular tissues at
the Fertility Preservation Program in Pittsburgh (https://fertilitypreservationpittsburgh.org/) donates a portion of
their tissue to research, which will enable us to extend the studies on macaques to human. SSC
transplantation is an established approach to regenerate spermatogenesis after gonadotoxic treatment, but
there are limitations to this method. This application will test three alternative approaches that may circumvent
some or all of these limitations. Aim 1 will test the hypothesis that co-administration of modulation of
granulocyte colony stimulating factor or fibroblast growth factor signaling at or around the time of gonadotoxic
treatment will enhance survival of endogenous SSCs and recovery of spermatogenesis. Aim 2 will build on our
recent demonstration that cryopreserved testicular tissue from prepubertal Rhesus macaques could be
autologously grafted under the back skin or scrotal skin of the same macaque or immunotolerant mice and
matured to produce sperm and a healthy baby. Graft recipients in those studies were peripubertal and
castrated. Since young fertility preservation patients will not be castrated and may not have tissues re-
implanted until adulthood, Aim 2 will confirm that immature testicular tissues can be matured in pubertal or
adult animals with intact testes. Immature human testicular tissues will also be grafted and matured in mouse
and monkey hosts. The limitations of the grafting approaches are the risk of reintroducing cancer cells if the
graft is done in human or exposure to xenotropic viruses if the graft is done in an animal. To circumvent these
issues, Aim 3 will utilize a testicular tissue organ culture, developed by Ogawa and colleagues, to mature
prepubertal testicular tissues ex vivo. This approach has not been replicated in mice or translated to other
species. We propose to replicate, modify and improve the Ogawa technique and compa...

## Key facts

- **NIH application ID:** 10165774
- **Project number:** 5R01HD100197-02
- **Recipient organization:** MAGEE-WOMEN'S RES INST AND FOUNDATION
- **Principal Investigator:** Marvin L. Meistrich
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $791,664
- **Award type:** 5
- **Project period:** 2020-05-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165774

## Citation

> US National Institutes of Health, RePORTER application 10165774, Next Generation Therapies for Fertility Preservation in Male Cancer Patients (5R01HD100197-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10165774. Licensed CC0.

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