Sex Differences in Lung Gas Volumes After Lipopolysaccharide-Induced Chorioamnionitis in Fetal Sheep

Abstract

Preterm female infants have a survival advantage and enhanced lung development, which is an important determinant of preterm survival. 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. 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. 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. Preterm female sheep fetuses had increased lung gas volumes after exposure to LPS, without any detectable differences in fetal inflammatory responses.