Synthetic oxytocin (sOT), known medically as Pitocin, is commonly used to induce or augment labor, while oxytocin-receptor antagonists (OTAs) are being developed to slow birth and prevent prematurity. Both sOT and OTAs are believed to cross the placental barrier. However, the effects of these maternal manipulations on infants remain largely unexplored, either in animal models or in humans. Project I will focus on the following objectives: (a) to develop and refine a new translational, animal paradigm, using the socially monogamous prairie vole, designed to model and allow the study of the consequences of birth interventions and taking into account possible effects on the mother-infant interaction;(b) to test the hypothesis that the presence or absence of OT at the time of birth will affect the behavior and nervous system (central and autonomic) of the offspring;and (c) to gain a deeper knowledge of mechanisms through which birth-related interventions may have lasting consequences. Specifically, we will examine the effects on offspring of (a) exposure during birth to sOT or (b) the effects of blocking endogenous OT (eOT), through the use of a selective OT antagonist (L-368,899). Project I will focus on behaviors (including alloparenting, partner preference formation, aggression, anxiety and depression) and neural processes (including the expression in brain tissue of genes for eOT and the related peptide, vasopressin), and selected receptors for each of these. In addition, autonomic processes in a subset of animals from these paradigms will be studied in adulthood. Animals created in Project 1 also will be studied in Project 11 (neural imaging). In addition, DNA from animals in Project I will be used in Project 111 to examine the hypothesis that alternations in OT in early life may have epigenetic consequences for DNA methylation.

Public Health Relevance

The widespread use of synthetic oxytocin (pitocin) to augment or induce birth continues although little is known regarding the consequences of such interventions for the offspring. The proposed study uses a paradigm that mimics current medical practice in a rodent model (the prairie vole) to evaluate the behavioral and physiological mechanisms through which birth interventions may have lasting consequences for the developing offspring. This research also has implications for our basic understanding ofthe developmental role of endogenous oxytocin, which is at present poorly understood. These findings can inform the development of methods to optimize human birth.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
1P01HD075750-01A1
Application #
8667728
Study Section
Special Emphasis Panel ()
Project Start
Project End
Budget Start
2014-04-11
Budget End
2015-02-28
Support Year
1
Fiscal Year
2014
Total Cost
$510,541
Indirect Cost
$114,897
Name
Northeastern University
Department
Type
DUNS #
001423631
City
Boston
State
MA
Country
United States
Zip Code
02115