Summary Although “fetal programming” has been extensively studied in many organs, there is only limited information on pulmonary effects in the offspring following intrauterine growth restriction (IUGR). We aimed to determine the effects of nutrient restriction on the lung structure and lung lipid differentiation programs in offspring using an animal mode of maternal food restriction (MFR). We utilized a rodent model of 50% MFR from day 10 of gestation to term and then using lung morphology, Western blotting, Real Time- RT-PCR and oil red O staining, lung structure and development of the offspring were examined at postnatal days (p) 1, p21, and 9 months (9M). At postnatal day 1, MFR pups weighed significantly less compared to control pups, but at p21 and 9M, they weighed significantly more. However, lung weight, expressed as a percentage of body weight between the two groups was not different at all time-points examined. The MFR group had significantly decreased alveolar number and significantly increased septal thickness at p1 and 9M, indicating significantly altered lung structure in the MFR offspring. Furthermore, although at p1, compared to the control group, lung lipid accumulation was significantly decreased in the MFR group, at 9M, it was significantly increased. There were significant temporal changes in the Parathyroid Hormone-related Protein/Peroxisome Proliferator-Activated Receptor gamma signaling pathway and surfactant synthesis. We conclude that MFR alters fetal lung lipid differentiation programming and lung morphometry by affecting specific epithelial-mesenchymal signaling pathways, offering the possibility for specific interventions to overcome these effects.

Patterns of fetal drinking behavior were quantified in five singleton fetuses (128 +/- 1 days gestation) by computer analysis of laryngeal-esophageal electromyography (EMG) and thoracic esophageal fluid flow. Esophageal flow was noted to be bidirectional with an average antegrade flow-to-retrograde flow ratio of 4.4 +/- 1.5. Retrograde esophageal flow coincided with diaphragmatic contractions, suggesting that inspiratory gastroesophageal pressure gradients may be operative. The regurgitated fluid was returned to the fetal rumen by thoracic esophageal contractions. Significant net fluid intake was noted during periods of primarily unidirectional antegrade esophageal flow. Fetuses swallowed an average of 35 +/- 9 ml/h during the 12-h study, extrapolating to an average daily volume of 840 +/- 224 ml. An EMG "propagated swallow" representing coordinated contractions of the thyrohyoid, nuchal esophagus, and thoracic esophagus averaged 43 +/- 3 swallows/h and was highly correlated with net esophageal flow. Nearly 60% of the total fluid intake occurred during "bouts" of propagated swallows, which represented only 8% of the study period. Bouts averaged 11.7 +/- 0.4 propagated swallows, lasted 2.1 +/- 0.2 min, and occurred every 27.6 +/- 1.7 min. Although EMG swallowing activity was similar, there were significant differences among fetuses in net esophageal fluid flow and volume per propagated swallow. We speculate that fetal fluid intake is dependent on the availability and physical properties of the swallowed fluid, whereas swallowing activity is primarily related to cortical maturation and thirst stimulation.