Fos response of fetal sheep anterior circumventricular organs to osmotic challenge in late gestation

We hypothesized that the anterior circumventricular organs (ACVO) and the supraoptic (SON) and hypothalamic paraventricular nuclei (PVN), among other structures that play a role in sensing extracellular body fluid volume and composition in postnatal animals (as demonstrated by Fos protein production by the immediate-early gene c-fos), would show similar activation in fetal sheep during an osmotic challenge. The brains of 10 fetal sheep [6 treated, 4 controls; 129-131 days of gestational age (dGA) = 0.87 gestation] were immunostained for Fos. Seventy-five minutes before tissue collection the dams were given intravenous 20% mannitol (1 ml · min^-1 · kg^-1 for 10 min). Subsequently, the ACVO, SON, and PVN were scored for the amount of neuronal Fos immunostaining. The subfornical organ (SFO; 24.5 ± 9.0 vs. 1.7 ± 1.2), the organum vasculosum of the lamina terminalis (OVLT; 26.8 ± 5.6 vs. 7.0 ± 2.0), the SON (39.8 ± 3.0 vs. 0.15 ± 0.1), and the PVN (59.8 ± 7.9 vs. 0.7 ± 0.7) had increases (P < 0.05) in the average number of Fos- positive cells per field compared with controls, whereas the median preoptic nucleus did not. Double immunostaining for Fos and arginine vasopressin (AVP) or oxytocin (OT) indicated that AVP- but not OT-immunopositive neurons in SON and PVN respond to osmotic challenge. These results demonstrate that the SFO, OVLT, SON, and PVN are activated by osmotic challenge in fetal sheep at 130 dGA.