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Pregnancy influences fetal brain development in a sex-dependent manner

Award Number: R01MH119459
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/10/2019
PERIOD OF PERFORMANCE END DATE: 01/31/2031

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Pregnancy influences fetal brain development in a sex-dependent manner - ABSTRACT Among pregnancy-associated complications, exposure to prenatal inflammation has been suggested to significantly influence fetal brain development. One interesting feature of neurodevelopmental disorders, including autism spectrum disorder (ASD), is their prevalence in males, which differs from autoimmune and inflammatory disorders that are more prevalent in females. In ASD, 4–5 times more boys develop ASD than girls. However, how fetal sex affects the vulnerability of developing brains to external stress, such as prenatal inflammation, is unknown. Using a rodent model of maternal immune activation (MIA), which my lab has extensively studied over the past decade, we aim to uncover the molecular underpinnings of why and how the same prenatal stress affects male, but not female, brain development. Our preliminary results indicate that the maternal immune system differentially affects the male-associated placenta. This forefront barrier tissue separates the fetal compartment (e.g., fetal brains) from pregnancy-associated stress. We have also identified sex-dependent changes in the expression of a receptor for the MIA-promoting cytokine, interleukin-17 (IL-17). In the proposed application, we will 1) investigate pregnancy-associated immunological changes in the maternal side and their interaction with placental tissues of male versus female fetuses to study their effects on fetuses’ cortical development and 2) determine the mechanisms by which fetal sex influences male-biased vulnerability to neurodevelopmental phenotypes with a focus on IL-17 receptor expression. Successful completion of the proposed study may provide explanations for the underlying mechanisms by which fetal sex and maternal immune factors influence neurodevelopment. The mechanistic understanding gained from this research can be applied to general knowledge of fetal brain development against developmental and environmental stresses in a sex-dependent manner.


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 = $722,358 )
2026	2026	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	6	5/11/2026	COMPETING CONTINUATION	$722,358
														Subtotal = $722,358

Issue Date FY: 2025 ( Subtotal = $0 )
2025	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	5	11/8/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2023 ( Subtotal = $635,425 )
2023	2023	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	5	6/9/2023	NON-COMPETING CONTINUATION	$635,425
														Subtotal = $635,425

Issue Date FY: 2022 ( Subtotal = $635,425 )
2022	2022	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	4	7/20/2022	NON-COMPETING CONTINUATION	$635,425
														Subtotal = $635,425

Issue Date FY: 2021 ( Subtotal = $627,374 )
2021	2021	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	3	6/24/2021	NON-COMPETING CONTINUATION	$627,374
														Subtotal = $627,374

Issue Date FY: 2020 ( Subtotal = $660,392 )
2020	2020	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	2	7/13/2020	NON-COMPETING CONTINUATION	$660,392
														Subtotal = $660,392

Issue Date FY: 2019 ( Subtotal = $660,392 )
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	001	1	9/24/2019	NEW	$0
2019	2019	PRESIDENT AND FELLOWS OF HARVARD COLLEGE	25 SHATTUCK ST	BOSTON	MA	02115	SUFFOLK	USA	Mental Health Research Grants	000	1	9/6/2019	NEW	$660,392
														Subtotal = $660,392

Grand Total All Awards = $3,941,366

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Pregnancy influences fetal brain development in a sex-dependent manner

Award Number: R01MH119459

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/10/2019

PERIOD OF PERFORMANCE END DATE: 01/31/2031

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