Intact osmoregulatory centers in the preterm ovine fetus: Fos induction after an osmotic challenge

We previously demonstrated a functional systemic dipsogenic response in the near-term fetal sheep (128-130 days; 145 days = full-term) with swallowing activity stimulated in response to central and systemic hypertonic saline. Preterm fetal sheep (110-115 days) do not consistently demonstrate swallow ing in response to hypertonic stimuli, and it is unclear whether this is du e to immaturity of osmoreceptor mechanisms or neuronal pathways activating swallowing motor neurons. To determine whether osmoreceptive regions in the preterm fetus are activated by changes in plasma tonicity, we examined Fos expression with immunostaining in these neurons in response to an osmotic challenge. Nine preterm fetal sheep [five hypertonic saline-treated fetuses (Hyp) and four isotonic saline-treated fetuses (Iso)] were prepared with v ascular and intraperitoneal catheters. Seventy-five minutes before tissue c ollection, hypertonic (1.5 M) or isotonic saline was infused (12 ml/kg) via an intraperitoneal catheter to fetuses. Brains were examined for patterns of neuronal activation (demonstrated by Fos protein expression). Hyp demons trated increases in plasma osmolality (similar to 10 mosmol/kg H2O) and Na concentrations (5 meq/l). Increased Fos expression was detected in Hyp in t he organum vasculosum of the lamina terminalis (OVLT), subfornical organ (S FO), median preoptic nucleus (MnPO), supraoptic (SON), and paraventricular nuclei (PVN) compared with Iso animals. Neuronal activation within the OVLT , SFO, and MnPO indicates intact osmoregulatory mechanisms, whereas activat ion of the SON and PVN suggests intact fetal neural pathways to arginine va sopressin neurons. These results suggest that preterm fetal swallowing inse nsitivity to osmotic stimuli may be due to immaturity of integrated motor n euron pathways.