Sex differences in avian embryo pulmonary surfactant production: evidence for sex chromosome involvement.
Sex differences in fetal pulmonary surfactant production have been shown in mammalian species, with the female at an advantage. A relationship between fetal sexual differentiation and the development of pulmonary surfactant production has been proposed. We hypothesized that if sex chromosomal factors play a role in causing the surfactant sex difference, then a reversal in the sex karyotype would be associated with a reversal in the surfactant sex difference and in some sex-specific responses to hormonal regulators of fetal surfactant production. To test this, we measured the surfactant-related phospholipids phosphatidylcholine and saturated phosphatidylcholine (SPC) in lung homogenates of avian embryos in which the male sex karyotype is homozygous (ZZ) and the female heterozygous (ZW). The following experimental groups were monitored: untreated controls on days 15 through 21 of gestation; embryos injected with 250 micrograms 17 beta-estradiol or of the antiestrogen CI 628; embryos injected with 250 micrograms testosterone or of the antiandrogen Flutamide; and embryos injected with 0.75 micrograms dexamethasone or 100 micrograms 11-deoxycortisol. Untreated controls exhibited significantly higher PC/milligram lung weight and SPC/milligram lung weight ratios in male embryos at gestation days 15 through 19. Hormone treatments also produced sex-specific effects. Dexamethasone significantly accelerated the male lung SPC concentration (35% over control) without affecting that of females. Glucocorticoid inhibition with 11-deoxycortisol significantly reduced the lung SPC concentration of both males and females, each by 19%. Testosterone significantly increased the female lung SPC concentration by 23%, and Flutamide significantly lowered this in the females by 24%. Estrogen reversed the sex difference by producing a relatively small (16%) decrease in the male lung SPC content while significantly increasing that of the females by 32%. CI 628 produced a modest and proportionate reduction of the lung SPC content in both sexes. These data provide evidence for a male advantage in fetal pulmonary surfactant production in the avian system, the reverse to that observed in humans, rabbits, rats, and mice. The known sex-specific responses of the developing surfactant system to glucocorticoids and to androgens are also reversed in the chick embryo as compared to the mammal. This gives additional support to the proposed link between the process of fetal sexual differentiation and the dimorphism in fetal pulmonary surfactant production and suggests that the sex chromosomes play an important regulatory role in the dimorphism of fetal surfactant production.
D000818:Animals; D002642:Chick Embryo; D003350:Cortodoxone / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005485:Flutamide / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism; D008297:Male; D009594:Nitromifene / Q000494:pharmacology; D010713:Phosphatidylcholines / Q000378:metabolism; D011663:Pulmonary Surfactants / Q000096:biosynthesis* / Q000235:genetics; D012730:Sex Chromosomes; D012733:Sex Differentiation; D013739:Testosterone / Q000494:pharmacology
D010713:Phosphatidylcholines; D011663:Pulmonary Surfactants; D013739:Testosterone; D004958:Estradiol; D009594:Nitromifene; D005485:Flutamide; D003907:Dexamethasone; D003350:Cortodoxone