Sex-related differences in cellular composition and surfactant synthesis of developing fetal rat lungs

Differences in pulmonary surfactant production by male and female fetuses in late gestation have been suggested, but the precise relationship of these findings to the changing cellular populations in the lung as development progresses has not been investigated previously. Using sexed rat littermates from Day 18 to 22 of gestation, we correlated the epithelial, endothelial, and interstitial cell composition of the lung with disaturated phosphatidylcholine (DSPC) content and with the incidence of lamellar bodies in epithelial cells and air sacs. At Days 19 and 20, female rat lungs had a higher content of DSPC than did the lungs of male littermates. At Days 20 and 21, more cuboidal epithelial cells of female fetuses contained lamellar bodies, and more air sacs in the female lung contained lipid material, than was observed in males. Sex-related differences in lung structure were seen even earlier. From Day 18 to Day 20, there was a greater proportion of epithelial cells in female lungs than in the lungs of male littermates; just before birth the cellular composition was similar. The results show that differentiation of epithelium with lamellar body formation and DSPC production occurs sooner in females. However, it is suggested that a sex-related difference in lung development occurs much earlier in the female at the onset of a phase of epithelial growth.