EFFECTS OF CHRONIC PLACENTAL INSUFFICIENCY ON BRAIN-DEVELOPMENT IN FETAL SHEEP

Clinical evidence has linked intrauterine compromise such as fetal hyp oxemia to poor neurologic outcome in the newborn. In this study we exa mined the effects of inducing chronic fetal hypoxemia by impairment of placental function on brain development in fetal sheep. Placental ins ufficiency was induced from 120 to 140 d of gestation (term = 145-148 d) by injection of microspheres into the umbilical circulation in five fetal sheep. Fetal partial pressure of oxygen, Pao,, was reduced from 24.1 +/- 0.5 mmHg before embolization to 14.8 +/- 0.4 mmHg after embo lization (p < 0.05), In another three fetuses a similar level of hypox emia (Pao(2), 13.8 +/- 0.4 mm Ag) occurred spontaneously. At 140 d of gestation the fetal brains were perfused with fixatives and compared w ith five control fetuses for the assessment of structural and immunohi stochemical alterations. Hyperemic fetuses demonstrated severe gliosis in the cerebral cortex and reduced myelination of subcortical white m atter as visualized by glial fibrillary acidic protein and myelin basi c protein staining, respectively (p < 0.05). White matter lesions were observed in two fetuses. The diameter of cerebral capillaries was inc reased in hypoxemic fetuses (p < 0.05), but there was no change in the number of nitric oxide synthase immunoreactive cells. Growth of neuro nal processes was affected in the cerebellum, where there was also a r eduction in the number of Purkinje neurons (p < 0.05). These results s how that a prolonged period of placental insufficiency, resulting in m oderate fetal hypoxemia during the last third of gestation, can affect neurodevelopmental processes that occur late in gestation such as mye lination and growth of the cerebellum. This prenatal damage could affe ct neural connectivity and have functional consequences after birth.