Sex differences in cardiorespiratory transition and surfactant composition following preterm birth in sheep

Male preterm infants are at greater risk of respiratory morbidity and mortality than females but mechanisms are poorly understood. Our objective was to identify the basis for the "male disadvantage" following preterm birth using an ovine model of preterm birth in which survival of females is greater than males. At 0.85 of term, fetal sheep underwent surgery (11 female, 10 male) for the implantation of vascular catheters to monitor blood gases and arterial pressure. After cesarean delivery at 0.90 of term, lambs were monitored for 4 h while spontaneously breathing; lambs were then euthanized and static lung compliance measured. We analyzed surfactant phospholipid composition in amniotic fluid and in bronchoalveolar lavage fluid (BALF) taken at necropsy; we also analyzed surfactant protein (SP) expression in lung tissue. Before delivery male fetuses tended to have lower pH (P = 0.052) compared with females. One hour after delivery, males had significantly lower pH and higher arterial partial pressure of CO₂ (Pa_CO2), lactate, glucose, and mean arterial pressure than females. Two males died 1 h after birth. Static lung compliance was 37% lower in males than females (P<0.05). In BALF, males had significantly more protein, a lower percentage of the phosphatidylcholine (PC) 32:0 (dipalmitoylphosphatidylcholine) and higher percentages of PC34:2 and PC36:2. There were no sex-related differences in lung architecture or expression of SP-A, -B, -C, and -D. The lower lung compliance in male preterm lambs compared with females may be due to altered surfactant phospholipid composition and function. These changes may compromise gas exchange and impair respiratory adaptation after male preterm birth.