Apoptosis in the Ovine Fetal Brain Following Placental Embolization and Intermittent Umbilical Cord Occlusion

Abstract

The purpose of this study was to compare the regional distribution of apoptotic cells in the near term ovine fetal brain caused by prolonged moderate hypoxia, as seen in placental insufficiency, and intermittent severe hypoxia, as seen in umbilical cord compression, which may then contribute to adverse neurodevelopment in the postnatal life. We hypothesized that apoptosis in the fetal brain will be increased in response to both prolonged moderate hypoxia and intermittent severe hypoxia. Twenty-one near term (126-127 days) sheep were divided into 3 groups: control (CON; n = 7), placental embolization (EMB; n = 7), and umbilical cord occlusion (UCO; n = 8). The EMB group had microsphere injections into the umbilical arterial circulation until the oxygen content was at 50% of baseline value. The UCO group had complete cord occlusion for 2 minutes every hour, 6 times a day for 2 consecutive days. At 4 pm on day 2, the animals were euthanized; fetal brains were fixed and prepared for apoptosis staining using the terminal uridine deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay method. In the cerebellar white matter, there was a 3-fold increase in the number of TUNEL positive cells per 1000 cells in both EMB and UCO animals as compared to CON (P = .017). There was also a significant increase in the frontal cortical grey matter (layers 1-3) in EMB animals as compared to CON (P = .014). As such, apoptosis in the near term fetal sheep brain is altered with both sustained moderate hypoxia and intermittent severe hypoxia in the latter part of pregnancy, with potential for long-term neurological sequelae.