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 CO(2) (Pa(CO(2))), 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.

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Preterm male infants have a higher incidence of morbidity and mortality due to respiratory insufficiency than females of the same gestational age. This male disadvantage could be due to differences in lung architecture; however, few studies have compared lung architecture in male and female fetuses during late gestation. Our principal objectives were to compare the morphology of the fetal lung and the maturity of the surfactant system in preterm male and female fetuses. Lungs from male (n = 9) and female (n = 11) fetal sheep were collected at 0.9 of term (131 days of the 145-day gestation) for morphological and molecular analyses. In separate groups, tracheal liquid was obtained from male (n = 9) and female (n = 9) fetuses at 0.9 of term for determination of surfactant phospholipid composition. We found no sex-related differences in body weight, lung weight, right lung volume, lung tissue and airspace fractions, mean linear intercept, septal crest density, septal thickness, the proportion of proliferating and apoptotic cells, and the percentages of collagen or elastin. The gene expression of surfactant protein -A, -B, -C, and -D and tropoelastin was similar between sexes. There were no differences in the proportion of the major phospholipid classes in the tracheal liquid between sexes; however there was a significantly higher percentage of the phospholipid species phosphatidylinositol 38:5 in males. The greater morbidity and mortality in preterm male lambs do not appear to be related to differences in lung structure or surfactant phospholipid synthesis before birth, but may relate to physiological adaptation to air-breathing at birth.

BackgroundAmong preterm infants, males have a greater incidence of respiratory distress and death than do females born at the same gestational age, likely due to sex-related differences in lung maturation. Our aim was to determine whether surfactant phospholipid composition differs between male and female preterm infants.MethodsGastric aspirate samples from male and female infants born between 25 and 30 weeks of gestation at The Royal Women's Hospital, Melbourne, Australia, were collected within 1 h after birth. Phospholipid composition was analyzed by electrospray ionization tandem mass spectrometry.ResultsPreterm males had higher proportions of total phosphatidylinositol (PI) and phosphatidylserine 36:2, lower proportions of total sphingomyelin (S) and S 33:1 and 35:1, and a greater phosphatidylcholine (PC)/S ratio than did females. The proportions of PC 30:0, PC 34:0, PC 34:2, PC 36:2, PC 36:3, and PC 38:2 differed between the sexes at different gestational weeks of birth; the proportion of PC 32:0 (dipalmitoylphosphatidylcholine) in males was lower than that in females at 25 weeks of gestation but higher at 27 weeks.ConclusionPhospholipid composition in pulmonary surfactant is different between male and female preterm infants of the same gestational age, which may contribute to the increased risk for respiratory morbidities in one sex.

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