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The Impact of Chronic Stress on Epigenetic Modifications in the Mother-Infant Dyad during Pregnancy

Award Number: R01MD017690
ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/25/2022
PERIOD OF PERFORMANCE END DATE: 06/30/2027

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The Impact of Chronic Stress on Epigenetic Modifications in the Mother-Infant Dyad during Pregnancy - Adverse maternal health outcomes remain a significant public health concern in the United States, contributing to elevated rates of maternal and infant morbidity and mortality. The underlying biological mechanisms contributing to these outcomes are not fully understood and may involve heritable factors, possibly mediated by epigenetic mechanisms. Recent studies have demonstrated that cumulative chronic stress and adversity may affect health outcomes through modifications to the epigenome, which can influence immune regulation, metabolic processes, cardiovascular function, and reproductive health. These stress-induced epigenetic modifications can be carried forward through the germline, to the potential detriment of successive generations. In this study, we seek to investigate how maternal stress and adversity influence distinct epigenetic modifications at the maternal-fetal interface that are linked to altered immune cell development, activation, and signaling in the placenta and developing offspring. The placenta regulates fetal immunity, conveys the maternal environment to the offspring, and is the gateway of epigenetic inheritance. Inherited genomic DNA forms the template for most biological inheritance, however epigenetic modifications can also persist across generations. Perturbed placental epigenetics is associated with intrauterine growth restriction, preterm birth, and pre-eclampsia, which are common drivers of infant morbidity and mortality. Recent studies demonstrate that chronic physiological stress is associated with chronic inflammation at the placenta and poor perinatal outcomes. However, the biological properties that shape these consequences during gestation remain unknown. We have expertise characterizing development of placental and fetal responses throughout gestation and have identified drivers of inflammation at the MFI associated with geno- and phenotypic immune alterations in the offspring. Thus, we hypothesize that chronic stress and adversity is transmitted across generations and manifests with epigenetic inheritance patterns that promote inflammation and innate immune dysfunction in the placenta and developing offspring. Three specific aims are proposed to interrogate our hypothesis: 1) Evaluate the burden of chronic stress and adversity on maternal systemic inflammation and epigenetic signatures; 2) Perform comparative transcriptional, epigenetic, and immunological profiling of term placental tissue to identify stress-associated molecular alterations; and 3) Investigate intrauterine programming of immune responses and the inheritance of specific epigenetic signatures in neonates exposed to maternal stress. Understanding the mechanisms linking maternal health and prenatal exposures to adverse perinatal outcomes and chronic disease risk across the lifespan is critical for developing prevention strategies and improving health trajectories across generations for all.


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 = $605,996 )
2025	2025	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	002	4	9/17/2025	NON-COMPETING CONTINUATION	$605,996
2025	2024	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	000	3	5/13/2025	TERMINATION	$0
2025	2024	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	001	3	9/12/2025	OTHER REVISION	$0
														Subtotal = $605,996

Issue Date FY: 2024 ( Subtotal = $597,833 )
2024	2024	THE MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	000	3	6/23/2024	NON-COMPETING CONTINUATION	$597,833
														Subtotal = $597,833

Issue Date FY: 2023 ( Subtotal = $616,322 )
2023	2023	MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	001	2	5/31/2023	NON-COMPETING CONTINUATION	$616,322
2023	2022	MOREHOUSE SCHOOL OF MEDICINE, INC.	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	000	1	5/16/2023	NEW	$0
														Subtotal = $616,322

Issue Date FY: 2022 ( Subtotal = $628,540 )
2022	2022	MOREHOUSE SCHOOL OF MEDICINE, INC., THE	720 WESTVIEW DR SW	ATLANTA	GA	30310	FULTON	USA	Minority Health and Health Disparities Research	000	1	9/25/2022	NEW	$628,540
														Subtotal = $628,540

Grand Total All Awards = $2,448,691

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The Impact of Chronic Stress on Epigenetic Modifications in the Mother-Infant Dyad during Pregnancy

Award Number: R01MD017690

ORGANIZATION: NATIONAL CENTER ON MINORITY HEALTH AND HEALTH DISPARITIES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/25/2022

PERIOD OF PERFORMANCE END DATE: 06/30/2027

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