Activation of cFos in Ovine Fetal Corticotropin- Releasing Hormone Neurons at the Time of Parturition*

Abstract

The ovine fetal pituitary adrenal axis plays an important role in parturition. While lesions of the paraventricular nucleus (PVN) in the fetal sheep delay parturition, suggesting that the PVN is necessary for the processes that lead up to parturition, evidence for stimulation of PVN neurons at time of delivery/labor is lacking. The present study tested the hypothesis that activation (evidenced by expression of the oncogene product cFos) of a specific population of PVN neurons containing CRH accompanies labor in sheep. Monitoring of uterine electromyogram activity determined the onset of labor. The brains of nine fetuses (removed by ceasarian section under anesthesia at gestational ages of 125-145 days) and four newborn sheep were perfused and stained for cFos and CRH. Before labor, less than 5% of fetal paraventricular CRH neurons expressed cFos. Verification that the CRH neurons could express cFos when adequately stimulated was made by exposing an additional group of four preterm animals (125 days gestational age) to hypoxemia; the six untreated fetuses served as controls. Activation of the CRH neurons by hypoxemia produced a rapid induction of cFos in CRH neurons, with approximately 50% of the cells strongly expressing cFos protein 1 h after exposure to hypoxia. At the time uterine contractions were first detected, 70% of CRH neurons expressed cFos, and cFos immunoreactivity persisted until just after birth. cFos staining declined rapidly, reaching prelabor levels in some animals by 2-3 h after birth. These data are consistent with the hypothesis that in addition to their potential role in the processes that initiate parturition over several days before birth, fetal CRH neurons are stimulated during labor, and termination of stimulation probably occurs rapidly after delivery.