Monday, June 30, 2025 6/30/2025

A-to-I RNA modifications in mouse oocytes

Award Number: R00HD099269
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: 08/26/2019
PERIOD OF PERFORMANCE END DATE: 02/28/2026

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A-to-I RNA modifications in mouse oocytes - PROJECT SUMMARY/ABSTRACT The primary objective of this proposal is to facilitate the development of Dr. Brachova into an independent research scientist. This objective will be accomplished through a combination of active mentorship, didactic training, enrichment activities, and research. The mentorship phase is well described by her mentors and includes weekly contact and formal course work. The core of the research focuses on the role of a post- transcriptional regulation mechanism known as RNA editing in overall oocyte quality. Defects in oocyte growth and meiotic maturation represent a significant cause of human birth defects, miscarriage, and infertility. The contribution of RNA post-transcriptional modifications is emerging as an important regulator of RNA stability and oocyte quality, however the role of adenosine deaminase acting on double stranded RNA (ADAR1), which catalyzes the deamination of an adenosine (A) into inosine (I) remains unexplored. The goal of this research is to determine the effect of ADAR1 RNA editing on RNA stability and oocyte competence in young and old mice. Preliminary data show that ADARFL/FLZP3-Cre oocytes have reduced embryonic developmental potential, suggesting that ADAR1 is a novel factor that contributes to female fertility. We also show that oocytes and eggs from aged individuals have reduced RNA editing efficiency, suggesting that RNA editing deficiencies could be involved in female age-associated decline of fertility. The central hypothesis is that ADAR1 RNA editing is a novel mechanism for maintaining female fertility through the regulation of RNA stability during oocyte growth and early embryonic development. The hypothesis will be tested in two independent specific aims. Specific Aim 1 will assess the role of ADAR1 A-to-I RNA editing in the regulation of maternal mRNA dosage in the oocyte and early embryo. Specific Aim 2 will determine how ADAR1 A-to-I RNA editing effects mRNA degradation in oocytes. The proposed research will utilize oocytes and eggs from young and maternally aged mice to explore the role of A-to-I editing in oogenesis and age-related reduction in fertility. This proposal represents an innovative approach to study oocyte competence, and has the potential to expand our understanding of female fertility. Furthermore, the studies proposed herein are integral to enhance the scientific training of Dr. Brachova and enable her to accomplish her goal of achieving independence and becoming an independent scientist in the field of female reproduction.


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	2024	OLD DOMINION UNIVERSITY	HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	001	6	3/20/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$84,749
2025	2024	OLD DOMINION UNIVERSITY	735 FAIRFAX AVE STE 909	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	000	5	3/20/2025	NON-COMPETING CONTINUATION	-$84,749
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $240,902 )
2024	2024	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	001	5	5/2/2024	NON-COMPETING CONTINUATION	$21,899
2024	2024	OLD DOMINION UNIVERSITY	HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	003	6	9/13/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$87,651
2024	2024	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	000	5	2/15/2024	NON-COMPETING CONTINUATION	$219,003
2024	2024	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	002	5	9/13/2024	NON-COMPETING CONTINUATION	-$87,651
2024	2024	OLD DOMINION UNIVERSITY	HAMPTON BLVD	NORFOLK	VA	23529	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	004	6	9/26/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
														Subtotal = $240,902

Issue Date FY: 2023 ( Subtotal = $245,717 )
2023	2023	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	000	4	2/16/2023	NON-COMPETING CONTINUATION	$245,717
														Subtotal = $245,717

Issue Date FY: 2022 ( Subtotal = $249,493 )
2022	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	000	3	3/25/2022	EXTENSION WITH OR WITHOUT FUNDS	$249,000
2022	2022	EASTERN VIRGINIA MEDICAL SCHOOL	735 FAIRFAX AVE STE 909C	NORFOLK	VA	23507	NORFOLK CITY	USA	Child Health and Human Development Extramural Research	001	3	6/22/2022	EXTENSION WITH OR WITHOUT FUNDS	$493
														Subtotal = $249,493

Grand Total All Awards = $736,112

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A-to-I RNA modifications in mouse oocytes

Award Number: R00HD099269

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: 08/26/2019

PERIOD OF PERFORMANCE END DATE: 02/28/2026

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