My research focuses on two global areas of both normal development and how the pregnancy environment [1] impacts fetal cardiovascular development and postnatal cardiovascular function; [2] impacts the pre and postnatal stress axis.
Together with Dr. Thomas McDonald, we have examined the role of the fetal brain in developing peripheral vascular tone. Using various techniques including immunocytochemistry for early gene activation and stereotaxic brain surgery, we have shown that regions within the brain that respond to changes in blood pressure in adult mammals do not activate to the same extent in fetuses. It appears that during 3/4 of fetal development endocrine modulation of blood pressure predominates. Closer to term, when the brain has undergone a period of significant growth, sympathetically mediated responses begin to provide the regulatory responses seen in adult animals.
Dr Yoshitaka Kimura (visiting scientist, Tohuka University, Japan) and Dr Matthias Loehle (postdoctoral fellow, University of Jena, Germany) have focused on the vascular reactivity of resistance arteries from both the fetal and maternal placentomal circulations in sheep. Using wire myography, we have shown that gestational changes in placental vascular reactivity from 78 to 135 days gestation (term 150 days) predominantly occur in fetal placentomal arteries. While the vascular smooth muscle of these vessels increases with gestation, responsiveness to circulating and locally released vasoconstrictive agents declines with advancing gestation. We believe that, after the period of rapid placental growth during early gestation, decreasing sensitivity of fetal placental arteries to vasoconstrictive agents, in combination with an increasing fetal cardiac output, may contribute to increased feto-placental blood flow in order to meet the increasing nutrient requirements of the growing fetus.
Together with Angela Rhoads (a University of Wyoming Research Associate), Matthias and Jeffrey Gilbert, we initiated studies of cardiovascular and stress responses in the male offspring of under nourished pregnancies when they reached 9 months of postnatal age. Maternal nutrient restriction resulted in hypertension (+17 mmHg compared to controls) and no change in heart rate with the animals at rest. In addition, the adrenal glands of the nutrient restricted offspring responded with increased cortisol production to both stimulation with CRH+AVP and the physiological stress of hypotension. Following slaughter we found a lower nephron number in the kidneys of the same group, and that nephron number correlated negatively with blood pressure in nutrient restricted animals only. Wall thickness of both the left and right ventricle of the heart was also increased in the wethers of nutrient restricted pregnancies. Taken together with our observations that the fetal heart is heavier halfway through nutrient restricted pregnancies, and that ventricle wall thickness is increased closer to delivery in nutrient restricted fetus, we now know that changes in the development of the heart persist following an origin in fetal life. Since nephron number is also reduced before birth, the same is true of the influence of maternal under nutrition on kidney development. These observations have provided direct evidence that nutrient deprivation during pregnancy has lasting effects on the offspring, despite re-alimentation half way through pregnancy and changes within the feto-placental circulation to maximize nutrient delivery to the fetus. |
