The distribution of FOS-immunoreactive neurons in the brainstem, midbrain and diencephalon of fetal sheep in response to acute hypoxia in mid and late gestation

FOS immunohistochemistry was used to map the distribution of neuronal pathways activated by hypoxia in fetal sheep. Conscious pregnant sheep were exposed to hypoxia (7-9% O(2), 1-2% CO(2), balance N(2)) for 2 h at either 100-105 days (n = 5) or 130-133 days gestation (n = 5); term is similar to 147 days. The hypoxia caused cessation of breathing movements at both fetal ages, and increased FOS staining in the medulla (area postrema, dorsal motor nucleus of vagus, nucleus solitary tract, ventrolateral medulla); pens (locus coeruleus and subcoeruleus, lateral and medial parabrachial nuclei); midbrain (habenula, periaqueductal grey, substantia nigra, areas ventrolateral to Red Nucleus); and hypothalamus (anterior and lateral hypothalamic areas, paraventricular and supraoptic nuclei). The results were essentially the same at both gestational ages, except that hypoxia increased FOS-staining in the habenula only in the older fetuses. The presence of FOS protein in pontomedullary cardiorespiratory nuclei at 100-105 days gestation indicates that the peripheral chemoreceptors respond to hypoxia at this early age, and in the subcoeruleus and medial parabrachial regions of the pens is consistent with lesion studies suggesting these areas mediate the inhibition of fetal breathing in response to hypoxia. FOS staining in the ventrolateral periaqueductal grey and habenula was unexpected, and suggests that pathways normally involved in response to noxious stimuli, or which are part of the hypothalamic 'defense' response are activated by hypoxia in the fetus. Some FOS-labelling could arise secondarily as a consequence of the cardiovascular and endocrine responses to hypoxia. (C) 1999 Elsevier Science B.V. All rights reserved.