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

Award Number: R01HD098278
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 05/31/2025

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


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $0 )
2026	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	5	11/24/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $597,648 )
2023	2023	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	5	6/1/2023	NON-COMPETING CONTINUATION	$597,648
														Subtotal = $597,648

Issue Date FY: 2022 ( Subtotal = $599,835 )
2022	2022	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90024	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	4	5/27/2022	NON-COMPETING CONTINUATION	$599,835
														Subtotal = $599,835

Issue Date FY: 2021 ( Subtotal = $605,349 )
2021	2021	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	3	5/26/2021	NON-COMPETING CONTINUATION	$605,349
														Subtotal = $605,349

Issue Date FY: 2020 ( Subtotal = $608,495 )
2020	2020	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	2	5/15/2020	NON-COMPETING CONTINUATION	$608,495
														Subtotal = $608,495

Issue Date FY: 2019 ( Subtotal = $635,331 )
2019	2019	UNIVERSITY OF CALIFORNIA, LOS ANGELES	10889 WILSHIRE BLVD STE 700	LOS ANGELES	CA	90095	LOS ANGELES	USA	Child Health and Human Development Extramural Research	000	1	5/27/2019	NEW	$635,331
														Subtotal = $635,331

Grand Total All Awards = $3,046,658

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

Award Number: R01HD098278

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 05/31/2025

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