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A rat model for induction and augmentation of labor with oxytocin
Abstract Number: O1-7
Abstract Type: Original Research
Introduction: Synthetic oxytocin (OXT) is widely used for both induction and augmentation of labor (IOL). Despite this widespread use, prevailing research is focused on the contractile effects of OXT and associated obstetric outcomes, and not much is understood about placental transfer of OXT and its effects on the fetus. A significant obstacle to generating high quality evidence is the lack of an appropriate animal model. Here, we report for the first time, a high-fidelity, clinically relevant rat model for labor induction and augmentation with OXT.
Methods: We created an innovative IOL model by implanting a microprocessor-controlled iPRECIO® pump (SMP-200, Primetech Corporation) subcutaneously in a near term pregnant rat (E21; term gestation E22.5) under brief isoflurane anesthesia, and tunneled the catheter to connect with a right internal jugular vein cannula (Fig 1). By internalizing the drug delivery system, pregnant rats were able to move freely without the risk of accidental disconnection. The preprogrammed pump was set to deliver escalating doses of OXT (Selleck Chemicals, 2 mg/mL in sterile NS; 400 μl total volume in reservoir) starting 2 h after post-surgical recovery. Duration of labor and survival of pups were recorded. To ensure external validity, we harvested the uterine myometrium to investigate contractility (phosphomyosin immunohistochemistry) and oxytocin receptor (OXTR) expression, and the lumbar spinal cord (L 2-4 segment) to investigate activation of nociception-related immediate early gene activation using c-Fos immunohistochemistry.
Results: After multiple iterations, we were able to induce labor and delivery using an OXT regimen that resembles clinical practice. Using the dose regimen described, delivery was accomplished between 12-18 h after initiation of OXT infusion. More than 80% of the pups survived birth. OXT infusion was accompanied by myometrial contraction as shown in Fig 2, significant downregulation of OXTR (Fig 3), and c-Fos expression in the lumbar spinal cord (Fig 4) suggesting that the induced contractions were painful. We are currently quantifying OXT pharmacokinetics, placental transfer of OXT, and intrauterine pressure during OXT infusion.
Conclusion: Our innovative IOL model will open critical lines of scientific inquiry related to pharmacological manipulation of labor. Future work is aimed at maternal-neonatal bonding and assessment of neurobehavioral outcomes in the offspring exposed to OXT in utero.