| Government
of Ontario/R. Howard Webster Foundation/Genesis Research
Foundation/Physiology Graduate Scholarship in Science
and Technology at the University of Toronto.
Thesis: Prenatal Stress, HPA Axis Function and Stress
Related behavior
Epidemiological evidence indicates
that poor fetal growth is associated with an increased
risk of a number of adult diseases, including hypertension
and type 2 diabetes mellitus. The link between fetal
growth and disease susceptibility involves the process
of fetal programming. This is a process by which a stimulus
encountered during critical windows of development can
have permanent effects on the structure and/or function
of physiological pathways, subsequently leading to pathological
consequences in adult life.
Glucocorticoids (GC), the end product
of hypothalamo-pituitary-adrenal (HPA) axis activation
are postulated to be a primary mediator of fetal programming.
Studies have revealed that exposure to GC in utero can
produce many of the symptoms observed in adults that
had poor prenatal growth, including permanently altered
basal and stress-induced HPA axis activity. Chronically
elevated levels of endogenous GC in the body can have
a number of adverse effects including decreased growth,
immunosuppression, and altered cardiovascular and behavioural
regulation. Modified regulation of the HPA axis, as
occurs in the process of fetal programming, also impairs
the ability of the organism to cope with physical and/or
psychological stress. Exposure to a stressor during
pregnancy results in activation of the maternal HPA
axis and consequently an influx of excess endogenous
GC of maternal origin to the fetus.
Studies have shown permanent and
sex-specific effects on pituitary-adrenal function of
offspring exposed to an acute period of nutrient restriction
or synthetic GC in utero. The aim of this study is to
understand the relationship between an altered maternal
environment and modified neuroendocrine and behavioural
function in adulthood. Specifically, how a moderate
maternal stress during pregnancy affects adrenocortical
development and subsequent activity. In addition, we
will identify how these changes modify stress-related
behaviour, learning and memory.
We hypothesize that prenatal stress
will have profound effects on HPA axis function in the
adult, but the specific nature and severity of the effect
will be dependent on gender and the timing of the stress.
This study will dissect and determine a number of the
mechanisms involved in the process of fetal neuroendocrine
programming, which represents a key link between adverse
intrauterine environment and susceptibility to disease
in adult life.
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