Does lung development differ in male and female fetuses?

Abstract

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.

Respiratory adaptation and surfactant composition of unanesthetized male and female lambs differ for up to 8 h after preterm birth

“…The pro-SP-C protein is synthesized by alveolar type II cells and is the precursor to mature SP-C, which facilitates the adsorption of surfactant lipids onto the surface film lining the alveoli, thereby assisting in preventing alveolar collapse (23,24). Taken together, and in the absence of any difference in lung architecture (25), these results confirm the notion that altered lung surfactant composition in males likely contributes to the greater incidence of respiratory distress syndrome in male preterm infants.…”

Physiological Adaptation among Preterm Infants and Associated Maternal Factors

“…However, the difference was not statistically significant probably due to the small sample size as this issue was not one of the main study objectives. The finding is in agreement with previous literature, and is often attributed to the higher susceptibility of male preterm infants to the respiratory distress syndrome problem [38] . This gender difference has been reduced by the use of continuous positive airway pressure [39] .…”

Maternal allergic asthma during pregnancy alters fetal lung and immune development in sheep: potential mechanisms for programming asthma and allergy

“…Lung structure and surfactant protein gene expression are similar in male and female sheep fetuses in late gestation (Ishak et al . ), and we saw no sex differences in the protective effects of surgically restricted placental growth and function (and hence restricted fetal growth) on later susceptibility to allergy in adolescent sheep in a previous study (Wooldridge et al . ).…”

“…One limitation of this study is that animal numbers were not sufficient to allow investigation of sex-specific responses. Lung structure and surfactant protein gene expression are similar in male and female sheep fetuses in late gestation (Ishak et al 2014), and we saw no sex differences in the protective effects of surgically restricted placental growth and function (and hence restricted fetal growth) on later susceptibility to allergy in adolescent sheep in a previous study (Wooldridge et al 2014). However, effects of maternal asthma on fetal growth in humans are sex-specific (Murphy et al 2003), and we therefore recommend that subsequent studies are powered to detect sex-specific effects of maternal asthma on fetal growth and development and progeny respiratory and immune function.…”