Sex differences in lung gas volumes after lipopolysaccharide-induced chorioamnionitis in fetal sheep

Background: Preterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival. Objective: Given the modulation of lung development by fetal exposure to infection/inflammation, we hypothesized that female fetuses have enhanced lung maturational responses to chorioamnionitis compared with male fetuses. Methods: Time-pregnant ewes received intra-amniotic injections with saline (n = 60) or lipopolysaccharide (LPS) at 2 days (n = 30) or 7 days (n = 45) before surgical delivery at 123 to 125 days of gestation (term: ∼147 days). We assessed inflammatory responses in bronchoalveolar lavage fluid and cord blood, lung maturation with pressure-volume curves, and lung structure. Results: Lung gas volume showed differences between the sexes after 2 days LPS (male 4.6 [1.2] mL/kg, female 7.7 [4.4] mL/kg; P = 0.02) and 7 days LPS (male 20.5 [9.3] mL/kg, female 27.0 [7.0] mL/kg; P = 0.01). The control group was not different by sex (male 8.0 [3.6] mL/kg, female 8.9 [3.9] mL/kg; P > 0.05). No difference in lung structure and in pulmonary and systemic inflammatory response was evident by sex. Conclusion: Preterm female sheep fetuses had increased lung gas volumes after exposure to LPS, without any detectable differences in fetal inflammatory responses.