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Elucidating the mechanism by which Elastin Microfibril interface-located protein 1 (EMILIN1) contributes to folliculogenesis

Award Number: F31HD116552
ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 09/16/2024
PERIOD OF PERFORMANCE END DATE: 09/15/2027

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Elucidating the mechanism by which Elastin Microfibril interface-located protein 1 (EMILIN1) contributes to folliculogenesis - PROJECT SUMMARY/ABSTRACT Premature ovarian insufficiency (POI) is characterized by a decline in ovarian function resulting in infertility and reduced ovarian hormone production. Globally, the rate of POI is approximately 3.5% resulting in ~138,250,000 women experiencing subfertility or infertility. Consequently, fertility preservation and restoration are a priority among patients with POI and individuals who desire children later in their reproductive lifespan. However, many limitations to the current fertility preservation and restoration options result in short hormonal functionality of transplanted ovarian tissue, low live birth rates, and low numbers of good-quality oocytes for in vitro maturation. Therefore, the development of novel technologies and methodologies for the advancement of reproductive science is imperative. Our main goal through this work is to elucidate matrisome-dependent mechanisms that contribute to folliculogenesis while also designing a defined biomaterial that improves follicle growth and oocyte quality in vitro. We will accomplish this through the interrogation of Elastin Microfibril Interface-located protein 1’s (EMILIN1) role in folliculogenesis (Aim 1) and by engineering a biomaterial that increases follicle growth and oocyte quality (Aim 2). Our preliminary studies demonstrate our ability to investigate matrisome-dependent cues in vitro using decellularized extracellular matrix (dECM) hydrogels derived from bovine ovarian tissue. We have shown that hydrogels with a high quantity of EMILIN1 increase murine follicle diameter in vitro compared to hydrogels with a low quantity of EMILIN1. This effect can be rescued with the addition of rhEMILIN1. Importantly, this effect can only be observed when follicles are cultured in dECM and EMILIN1 had no effect on growth when added to a biologically inert hydrogel, alginate. Therefore, we will elucidate the mechanism by which EMILIN1 increases follicle growth by performing bulk-RNA sequencing on murine follicles grown in the presence or absence of EMILIN1 in dECM and interrogating the signaling pathways associated with EMILIN1. Then, we will engineer a hydrogel of defined matrisome composition to recapitulate the follicle growth dynamics observed in dECM hydrogels with an abundance of EMILIN1. To do this, we will perform a co-immunoprecipitation (co-IP) and subsequent unbiased proteomics to define matrisome proteins that EMILIN1 associates with. We will then use this list of proteins to design an ECM hydrogel for ovarian follicle culture that increases follicle growth and oocyte quality via an EMILIN1-driven mechanism. Taken together, these aims will expand our understanding of the role of EMILIN1 in folliculogenesis, advise future work in designing advanced biomaterials for follicle culture, and lead to future fertility preservation and restoration options. Finally, this research will be influential to the greater scientific community by expanding our technical repertoire for studying matrisome-dependent biochemical cues within other organ systems.


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 = $45,327 )
2026	2026	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	3	8/10/2026	NON-COMPETING CONTINUATION	$45,327
														Subtotal = $45,327

Issue Date FY: 2025 ( Subtotal = $44,751 )
2025	2025	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	2	8/8/2025	NON-COMPETING CONTINUATION	$44,751
														Subtotal = $44,751

Issue Date FY: 2024 ( Subtotal = $44,187 )
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	001	1	9/23/2024	NEW	$0
2024	2024	ANN & ROBERT H LURIE CHILDRENS HOSPITAL OF CHICAGO	225 E CHICAGO AVE	CHICAGO	IL	60611	COOK	USA	Child Health and Human Development Extramural Research	000	1	9/16/2024	NEW	$44,187
														Subtotal = $44,187

Grand Total All Awards = $134,265

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Elucidating the mechanism by which Elastin Microfibril interface-located protein 1 (EMILIN1) contributes to folliculogenesis

Award Number: F31HD116552

ORGANIZATION: NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 09/16/2024

PERIOD OF PERFORMANCE END DATE: 09/15/2027

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