Date of Award

Spring 2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Committee Director

R. James Swanson

Committee Member

Christopher Osgood

Committee Member

Lesley Greene

Abstract

Every year more than 75,000 pregnant women are exposed to teratogenic medications or general anesthesia during non-obstetric surgery in the US,1-4 and embryonic effects of general anesthesia are of particular interest in laboratory research and veterinary medicine. The mouse system is used to screen potential toxic effects of anesthetics used in egg retrieval for in vitro fertilization (IVF), or those of pharmacologic agents which may come in contact with the egg or early embryo. Mouse preimplantation 2-cell embryos were exposed in vitro to incremental concentrations of common general anesthetics within and exceeding the normal clinical dosage range for mice (propofol 50-200mg/kg, sodium pentobarbital 50mg/kg, and ketamine hydrochloride 50-100mg/kg) for 72h to determine the effects of each anesthetic on subsequent cleavage and development during prolonged exposure. The anesthetic dosage ranges were as follows: propofol 0-25.0μg/mL, sodium pentobarbital 0-300µg/mL, and ketamine hydrochloride 0-5000µg/mL, embryonic development was evaluated every 24h during the 72h mouse embryo assay culture period. Results found propofol (≥2.01μg/mL), sodium pentobarbital (≥30μg/mL), and ketamine hydrochloride (≥40μg/mL) to exert inhibitory effects to the in vitro development of preimplantation mouse embryos. The percentage of 2-cell embryos developing to more advanced stages was decreased by exposure to higher concentrations of all three compounds. By the 72h endpoint, blastomeres of delayed and arrested embryos began to degenerate, displaying lysis and/or fragmentation; embryos exposed to lower concentrations of each anesthetic demonstrated a significant ability to continue cleavage and differentiation towards blastocyst formation. Conclusion: Embryotoxic effects to preimplantation embryos were observed in a dose-dependent manner after 72h of in vitro culture with propofol, sodium pentobarbital. and ketamine hydrochloride.

Comments

Dissertation Submitted to the Faculty of Eastern Virginia Medical School and Old Dominion University in Partial Fulfillment of the Requirement for the Degree of Doctor of Philosophy in Biomedical Sciences.

DOI

10.25777/k9ed-gn11

ISBN

9781339123554

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