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Role of dopamine in neuroimmunoendocrine mechanisms of spontaneous preterm birth

Award Number: R01HD121701
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: 05/15/2026
PERIOD OF PERFORMANCE END DATE: 02/28/2031

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Role of dopamine in neuroimmunoendocrine mechanisms of spontaneous preterm birth - SUMMARY Reliable tools for early prediction and effective treatments of spontaneous preterm birth (sPTB) are missing. This is due to an incomplete understanding of the subclinical pathobiology preceding sPTB. The long-term goal of this project is to integrate pathological, physiological, and psychological domains preceding sPTB to define mind- body crosstalk mechanisms that enable robust sPTB prediction and reveal potential targets for therapeutic intervention. The overall objective in this application is to establish neuroimmunoendocrine pathways as critical modulatory links between maternal mental state, immune imbalance, and sPTB. The central hypotheses are that (i) catecholaminergic (i.e., dopaminergic) signaling in maternal central and peripheral systems mitigates inflammation-induced parturition, supporting pregnancy maintenance, and that (ii) disruptions in neuroendocrine signaling may underlie an immune shift in the maternal circulation as well as at the maternal-placental interface promoting sPTB. The central hypotheses will be tested by pursuing three specific aims: 1) Determine whether central dopaminergic activity mitigates inflammation-induced PTB in mice; 2) Define predictive neuroimmunoendocrine trajectories of sPTB and their placental inflammatory signatures; and 3) Determine the effect of dopamine on the human maternal-placental interface, comparing sPTB vs. TB. Under the first aim, an established murine model of PTB will be combined with targeted neuromodulation of central reward circuitry to evaluate the effect on birth timing and peripheral immune state. In the second aim, human pregnancies at risk for sPTB will be longitudinally evaluated for multiple psychological (psychometric surveys, allostatic load) and physiological (blood immune function, non-invasive urine markers, cerebrospinal fluid markers, placental pathology) domains to define mind-body crosstalk prior to and at manifestation of clinical parturition pathology. In aim three, human endometrial stromal cells will be used to identify and causally link the effect of catecholamines on inflammatory signaling, differentiation, and protein secretion at the maternal-placental interface. The research proposed in this application is innovative because it represents a substantive advancement from the status quo by defining the basic principles of the maternal brain–immune–reproductive system axis in healthy pregnancies and those complicated by sPTB. The proposed research is significant because it is expected to offer a strong scientific framework whereby new strategies for the clinical management of patients at risk for sPTB can be developed.


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 = $657,971 )
2026	2026	UNIVERSITY OF CALIFORNIA, SAN DIEGO	9500 GILMAN DR	LA JOLLA	CA	92093	SAN DIEGO	USA	Child Health and Human Development Extramural Research	000	1	5/14/2026	NEW	$657,971
														Subtotal = $657,971

Grand Total All Awards = $657,971

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Role of dopamine in neuroimmunoendocrine mechanisms of spontaneous preterm birth

Award Number: R01HD121701

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: 05/15/2026

PERIOD OF PERFORMANCE END DATE: 02/28/2031

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