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Effects of the ovarian mechanical properties on folliculogenesis

Award Number: R01HD120348
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: 08/01/2026
PERIOD OF PERFORMANCE END DATE: 03/31/2031

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Effects of the ovarian mechanical properties on folliculogenesis - SUMMARY Reproductive aging is associated with declines in follicle number, oocyte quality, and production of the ovarian hormones estrogen and progesterone. The cessation of ovarian function at menopause is associated with multiple pathologies, such as osteoporosis, because ovarian hormones regulate many tissues, resulting in an acceleration of overall aging. One hallmark of ovarian aging in mice and humans is increased inflammation in the ovarian stroma and follicles. However, the mechanisms driving follicle inflammation are not fully known, hampering the development of novel treatment strategies to preserve female reproductive health. One common outcome of inflammation is increased tissue stiffness, driven by remodeling of the extracellular matrix. With age, mouse and human ovaries become stiffer, and microenvironment stiffness impairs follicle development and oocyte quality. In addition, environment stiffness induces an inflammatory response in the follicle. Therefore, this proposal tests the overarching hypothesis that follicles irreversibly detect the age-associated increase in ovarian stiffness and respond by producing inflammatory molecules, creating a positive feedback loop that impairs oocyte quality, ovarian function and fertility. This hypothesis will be tested in three specific aims. Aim 1 is to define the contribution of microenvironment stiffness to the age-associated increase in follicle inflammation. Aim 2 is to determine the effects of irreversibly integrating mechanical inputs on follicle function. Aim 3 is to determine the effects of ovarian stiffness on oocyte quality and fertility in vivo. These aims will provide a comprehensive and integrated molecular mechanism of the stiffness-derived changes in ovarian function. In the long term, data from these studies may allow development of new strategies to reverse or delay ovarian aging by targeting mechanotransduction pathways.


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 = $461,435 )
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Child Health and Human Development Extramural Research	000	1	5/7/2026	NEW	$461,435
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Child Health and Human Development Extramural Research	001	1	5/14/2026	NEW	$0
2026	2026	WASHINGTON UNIVERSITY, THE	1 BROOKINGS DR	SAINT LOUIS	MO	63130	SAINT LOUIS	USA	Child Health and Human Development Extramural Research	002	1	7/2/2026	NEW	$0
														Subtotal = $461,435

Grand Total All Awards = $461,435

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Effects of the ovarian mechanical properties on folliculogenesis

Award Number: R01HD120348

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: 08/01/2026

PERIOD OF PERFORMANCE END DATE: 03/31/2031

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