Alterations in fetal and placental deoxyribonucleic acid synthesis rates after chronic fetal placental embolization

OBJECTIVE: Fetal growth and development are closely related to normal placental growth and function. We performed a study to determine the effect of a 10-day period of fetal hypoxemia induced by umbilical-placental hypoperfusion on tissue deoxyribonucleic acid synthesis rates in the 0.84 to 0.91 of gestation ovine fetus and placenta. STUDY DESIGN: Daily fetal placental embolization was performed in four chronically catheterized sheep fetuses until fetal arterial oxygen content decreased by 30% compared with preembolization values. Five control fetuses received vehicle only. On experimental day 10, the deoxyribonucleic acid synthesis rate was determined by injecting tritiated thymidine (1 mCi/kg) intravenously approximately 8 hours before the end of the study. RESULTS: Fetal arterial oxygen decreased from 3.2 ± 0.1 (SEM) mmol/L preembolization to 2.2 ± 0.2 mmol/L on day 10 (p< 0.001) and remained unchanged in controls. On day 10 deoxyribonucleic acid synthesis rates were significantly reduced in embolized fetuses compared with controls, by 38% in cotyledons (83.0 ± 15.1 vs 133.7 ± 9.9 disintegrations/min/μg deoxyribonucleic acid, (p< 0.05), 28% in the left ventricular wall (36.8 ± 3.7 vs 51.0 ± 4.7 disintegration/min/μg deoxyribonucleic acid, p< 0.05), and 45% in the quadrieps muscle (15.4 ± 4.0 vs 28.1 ± 3.0 disintegration/min/μg deoxyribonucleic acid, p< 0.05). Tritiated thymidine autoradiography demonstrated that cotyledonary deoxyribonucleic acid synthesis occurred exclusively in the fetal trophoblasts cells. CONCLUSION: We concluded that a reduction in cotyledonary, quadriceps muscle, and left ventricular myocardium deoxyribonucleic acid synthesis rates are the earliest adaptive mechanisms of fetal growth associated with development of umbilical-placental insufficiency. We speculate that alteration in the myocardial deoxyribonucleic acid synthesis rate could be a major contributing factor in the deterioration of fetal myocardial function associated with increased placental vascular resistance.