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The actions of steroid hormones on oviduct function

Award Number: R01HD097087
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: 08/10/2022
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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The actions of steroid hormones on oviduct function - PROJECT SUMMARY/ABSTRACT Approximately 14% of infertility cases that undergo assisted reproductive technologies (ART) are due to Fallopian tube dysfunction. In 2015 alone, over 230,000 ART cycles were performed in the U.S, yet, less than 30% of those cycles resulted in pregnancy. Moreover, the incidence of epigenetic disorders is increased in in vitro-conceived embryos. A major contributing factor to the poor success and inherent problems associated with ART is our lack of understanding of the nature of the oviductal environment. Attempts to improve culture media by mimicking the oviductal environment, however, have been limited by our lack of understanding of the optimal microenvironment provided by the oviduct and how it changes during the course of preimplantation embryo development. Therefore, our long-term goal is to identify the key factors produced by each epithelial cell type that are crucial for sperm migration, fertilization, embryo development, and embryo transport. It has been established that ovarian-derived steroid hormones, estrogen (E2) and progesterone (P4), modulate the function of epithelial cell lining of the oviduct. However, how steroids modulate the function of these epithelial cell populations that are tailored for each specific stage during pregnancy establishment is undefined. As such, in this study, we will develop a spatiotemporal map of steroid actions and their effect on oviductal epithelial cells during the course of sperm/embryo transport and embryo development. Specifically, using mouse models, we will determine how E2 and P4 mediate distinct populations of epithelial cells of the oviduct to create an appropriate milieu that changes at different points in time during the course of pre-implantation embryo development. Our central hypothesis is that fine-tuning of the oviductal epithelium through the actions of E2 and P4 allows the oviduct to create a malleable environment that supports fertilization and responds to the changing metabolic needs of developing embryos. We propose to: determine the roles of 1) E2 and 2) P4 signals through their classical nuclear receptor either in the secretory or the ciliated epithelial cell of the oviduct during the sperm migration, the time of fertilization, pre-implantation embryo development, and embryo transport. Also, 3) gene expression profile corresponding to E2 and P4 action in epithelial cell populations at different regions of the oviduct and at distinct stages will be defined at a single cell resolution using mouse models. The successful completion of these aims will fill fundamental gaps in knowledge for two main reasons. First, the information will provide novel insight into the molecular mechanisms driving oviductal functions. Second, understanding which cell populations function during each stages of sperm/embryo transport and embryo development will generate much needed information to optimize culture conditions in an ART setting.


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: 2025 ( Subtotal = $0 )
2025	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Child Health and Human Development Extramural Research	000	6	1/14/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	4	7/12/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $309,982 )
2023	2023	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Child Health and Human Development Extramural Research	002	6	2/16/2023	NON-COMPETING CONTINUATION	$317,483
2023	2022	UNIVERSITY OF MISSOURI SYSTEM	121 UNIVERSITY HALL	COLUMBIA	MO	65211	BOONE	USA	Child Health and Human Development Extramural Research	001	5	11/28/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$224,725
2023	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	4	11/28/2022	NON-COMPETING CONTINUATION	-$232,226
														Subtotal = $309,982

Issue Date FY: 2022 ( Subtotal = $311,875 )
2022	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	4	2/2/2022	NON-COMPETING CONTINUATION	$280,687
2022	2022	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	001	4	4/20/2022	NON-COMPETING CONTINUATION	$31,188
														Subtotal = $311,875

Issue Date FY: 2021 ( Subtotal = $355,576 )
2021	2021	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	3	2/17/2021	NON-COMPETING CONTINUATION	$355,576
														Subtotal = $355,576

Issue Date FY: 2020 ( Subtotal = $399,104 )
2020	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	001	2	5/13/2020	SUPPLEMENT FOR EXPANSION	$44,144
2020	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	2	2/21/2020	NON-COMPETING CONTINUATION	$354,960
2020	2020	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	002	2	5/19/2020	SUPPLEMENT FOR EXPANSION	$0
														Subtotal = $399,104

Issue Date FY: 2019 ( Subtotal = $359,943 )
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	001	1	8/24/2019	SUPPLEMENT FOR EXPANSION	$40,439
2019	2019	WASHINGTON STATE UNIVERSITY	240 FRENCH ADMINISTRATION BLDG	PULLMAN	WA	99164	WHITMAN	USA	Child Health and Human Development Extramural Research	000	1	3/12/2019	NEW	$319,504
														Subtotal = $359,943

Grand Total All Awards = $1,736,480

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The actions of steroid hormones on oviduct function

Award Number: R01HD097087

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: 08/10/2022

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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