Intrauterine growth restriction delays surfactant protein maturation in the sheep fetus

Abstract

Pulmonary surfactant is synthesized by type II alveolar epithelial cells to regulate the surface tension at the air-liquid interface of the air-breathing lung. Developmental maturation of the surfactant system is controlled by many factors including oxygen, glucose, catecholamines, and cortisol. The intrauterine growth-restricted (IUGR) fetus is hypoxemic and hypoglycemic, with elevated plasma catecholamine and cortisol concentrations. The impact of IUGR on surfactant maturation is unclear. Here we investigate the expression of surfactant protein (SP) A, B, and C in lung tissue of fetal sheep at 133 and 141 days of gestation (term 150 +/- 3 days) from control and carunclectomized Merino ewes. Placentally restricted (PR) fetuses had a body weight <2 SD from the mean of control fetuses and a mean gestational Pa(O(2)) <17 mmHg. PR fetuses had reduced absolute, but not relative, lung weight, decreased plasma glucose concentration, and increased plasma cortisol concentration. Lung SP-A, -B, and -C protein and mRNA expression was reduced in PR compared with control fetuses at both ages. SP-B and -C but not SP-A mRNA expression and SP-A but not SP-B or -C protein expression increased with gestational age. Mean gestational Pa(O(2)) was positively correlated with SP-A, -B, and -C protein and SP-B and -C mRNA expression in the younger cohort. SP-A and -B gene expression was inversely related to plasma cortisol concentration. Placental restriction, leading to chronic hypoxemia and hypercortisolemia in the carunclectomy model, results in significant inhibition of surfactant maturation. These data suggest that IUGR fetuses are at significant risk of lung complications, especially if born prematurely.

Ventilation-induced lung injury is not exacerbated by growth restriction in preterm lambs

“…This is in contrast to previous studies showing significantly reduced PC content and lower lung volume in growth-restricted rats (13). In sheep, growth restriction resulted in decreased surfactant protein (41), which was speculated to result from glucocorticoid and hypoxic signaling pathways (42). Importantly, none of these studies have looked at levels of PC in the airway lumen (e.g., in BALF).…”

The effects of intrauterine growth restriction and antenatal glucocorticoids on ovine fetal lung development

“…The differences between these experimental models of IUGR most likely reflect the timing of IUGR, rather than the method of inducing IUGR. Because glucocorticoids induce the production of SPs (21,22), the hypercortisolemia induced by IUGR in this and other studies (18)(19)(20) would be expected to increase SP mRNA expression. Another known regulator of SPs is fetal oxygenation (23).…”

“…In contrast, in a recent study where carunclectomy was used to induce IUGR, a reduction in fetal lung expression of SP-A, SP-B, and SP-C mRNA was reported (20). The differences between these experimental models of IUGR most likely reflect the timing of IUGR, rather than the method of inducing IUGR.…”

Correlation of fetal middle cerebral artery Doppler indices in IUGR pregnancies

“…Intrauterine growth restriction (IUGR) defined by body mass and weight loss less than 10th percentile is regarded as dangerous pregnancies due to complications resulted from delivery interventions in mother and later neonatal complications 1,2 . A quick, easy and accurate method of estimation of fetal growth in utero would be of obvious benefit to the clinician practic ing the modern obstetrics.…”