# Towards a preclinical model for overcoming infertility with induced pluripotent stem cells

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $597,648

## Abstract

Summary
Around 12% of women in the United States have problems getting pregnant and carrying a baby to term, with
7% of women and their partners being diagnosed as infertile. Some diagnoses of infertility can be overcome
through Assisted Reproductive Technologies (ART), however these technologies require each partner to make
functional gametes (eggs or sperm) for success. For those individuals incapable of making gametes, ART is
not an option for overcoming a diagnosis of infertility. In this grant, we are developing a model for fertility
restoration to the infertile patient using induced pluripotent stem cells (iPSCs). This basic research proposal is
aimed at testing the hypothesis that prenatal and neonatal gonadal somatic cells are required to instruct male
and female germline cell differentiation using non human primate (NHP) iPSCs. The proposal under
consideration is based upon the scientific premise with mouse (m) models that male and female miPSCs
differentiated into mouse primordial germ cell (PGC)-like cells (mPGCLCs) will undergo sex-specific
differentiation when transplanted with prenatal gonadal somatic cells, or directly into neonatal niches. The
success of this technology in the mouse was first built upon a fundamental understanding of mouse germline
cell development, particularly during prenatal life. Here, we propose three aims in which we will use
developmental biology, genomics and transplantation to understand the cell and molecular basis of sex-
specific PGC differentiation in vivo using NHPs. This knowledge will be used to differentiate male and female
NHP iPSCs towards PGCLCs that can undergo sex-specific differentiation using the signaling logic of the
prenatal gonad, or alternatively following transplantation or culture with prenatal or neonatal gonadal somatic
cells. At the conclusion of this proposal, we will have determined the extent to which NHP PGCLCs are
capable of sex-specific differentiation within prenatal and neonatal gonadal niches. This work will be used to
inform future studies aimed at recreating male and female gametogenesis from NHP's entirely in vitro.

## Key facts

- **NIH application ID:** 10630112
- **Project number:** 5R01HD098278-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Amander Clark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $597,648
- **Award type:** 5
- **Project period:** 2019-06-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630112

## Citation

> US National Institutes of Health, RePORTER application 10630112, Towards a preclinical model for overcoming infertility with induced pluripotent stem cells (5R01HD098278-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10630112. Licensed CC0.

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