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Human Placental Morphology, Function, and Pathology: Relationship to Environmental Exposures and Newborn and Child Health

Award Number: R01ES029281
ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2018
PERIOD OF PERFORMANCE END DATE: 04/30/2025

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Human Placental Morphology, Function, and Pathology: Relationship to Environmental Exposures and Newborn and Child Health - PROJECT SUMMARY/ABSTRACT Metal exposures are common as are their pernicious effects on human health. Of greater concern are their actions on the vulnerable developing fetus. However, even though the placenta is available from every delivery, few are routinely evaluated. Therefore, we continue to lack sufficient information regarding the mechanisms by which prenatal metals exposures harm the fetus, key steps along the path towards early identification of the at-risk fetus, and intervention to optimize childhood and lifelong wellbeing. There is growing evidence that the intrauterine environment impacts placental development and function to ultimately influence the risk of obesity in offspring. Childhood overweight and obesity are common and important predictors of morbidity and mortality across the life course. The goal is to determine, in a unique, established cohort in which all-placentas were studied and have placental tissue archived, how placental health and function are affected by metal exposures, and the pathways that lead from metals exposures and placental toxicity to altered infant somatic growth and metabolism. Finally, the clinical results will be validated with in vitro explant studies of human placentas, in which metals exposures can be tested for induction of placental cell specific responses. Starting with cutting edge methods that identify, quantitate and localize to specific cell types metals that accumulate in the placenta across gestation, we will use archived placental tissues further to identify placental pathology (including cell proliferation, apoptosis, inflammation and endothelial or macrophage activation) by traditional histologic and immunohistochemical methods, pairing slide digitization and automated custom software algorithms that register serial digitized placental tissue slides to match placental lesions to the presence, quantity and type of metals. Together with maternal, gestational and neonatal data extracted from the electronic medical record, we will move to analyses of newborn dried blood spots collected and archived as part of the Newborn Screening Program of New York State to test for serum markers of inflammation that may result from metals exposures and placental toxicity, and a metabolic profile that we will correlate with placental size, newborn size, and serial child weight for length centiles and growth trajectory to 12 months of age. Lastly our large sample size of 2000 mother-child-placenta triads will allow us to explore sex-dependent effects of metals toxicity in the placenta and in the child. The methods in this proposal provide unprecedented interrogation of the placenta’s role in fetal pathophysiology of metals toxicity, and the development of obesity at age 1 year, a strong predictor of other health risks including obesity, diabetes and cardiovascular disease.


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	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	5	8/28/2025	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	001	5	5/17/2024	SUPPLEMENT FOR EXPANSION	$0
2024	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	5	5/16/2024	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $525,419 )
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	001	5	6/8/2022	NON-COMPETING CONTINUATION	$416,774
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	4	1/28/2022	SUPPLEMENT FOR EXPANSION	$30,241
2022	2022	RESEARCH FOUNDATION FOR MENTAL HYGIENE INC	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	002	5	6/17/2022	SUPPLEMENT FOR EXPANSION	$78,404
														Subtotal = $525,419

Issue Date FY: 2021 ( Subtotal = $504,773 )
2021	2021	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	4	5/11/2021	NON-COMPETING CONTINUATION	$504,773
														Subtotal = $504,773

Issue Date FY: 2020 ( Subtotal = $520,488 )
2020	2020	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	3	5/29/2020	NON-COMPETING CONTINUATION	$520,488
														Subtotal = $520,488

Issue Date FY: 2019 ( Subtotal = $458,852 )
2019	2019	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	2	5/1/2019	NON-COMPETING CONTINUATION	$458,852
														Subtotal = $458,852

Issue Date FY: 2018 ( Subtotal = $495,514 )
2018	2018	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	1050 FOREST HILL RD	STATEN ISLAND	NY	10314	RICHMOND	USA	Environmental Health	000	1	6/26/2018	NEW	$495,514
														Subtotal = $495,514

Grand Total All Awards = $2,505,046

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Human Placental Morphology, Function, and Pathology: Relationship to Environmental Exposures and Newborn and Child Health

Award Number: R01ES029281

ORGANIZATION: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2018

PERIOD OF PERFORMANCE END DATE: 04/30/2025

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