Developmental Toxicology

Lab head: Helen Ritchie
Location: Anderson Stuart Building

Lab members: William S Webster Diana Oakes Andrew Howe

Why does phenytoin cause birth defects ?

Primary supervisor: Helen Ritchie

Our laboratory is interested in why some drugs taken during pregnancy cause birth defects. We use rat models to answer this question. Phenytoin is a drug used to control epilepsy. However it causes cleft lip in humans if taken during pregnancy. The mechanism by which phenytoin causes birth defects remains unknown but there is a strong hypothesis that phenytoin that crosses the placenta slows the embryonic heart causing the fetus to become hypoxic for some hours.   If this hypoxia occurs during critical periods of facial development it is thought to induce abnormal development.   We are going to test this hypothesis by examining the heart rate of the embryo in vivo by ultrasound and in vitro by embryo culture.  There is an alternate hypothesis which proposes that the malformations are caused by hyperglycaemia.  We will test this hypothesis by measuring the glucose levels in pregnant rats following a teratogenic dose of phenytoin.

Discipline: Biomedical Sciences
Co-supervisors: William Webster, Diana Oakes
Keywords: toxicology, Birth defects, developmental biology