Syntaxin 1A is transiently expressed in fetal lung mesenchymal cells: potential developmental roles.

Lung development is a complex process in which epithelial-mesenchymal interactions play a key role. A conserved secretory apparatus, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, is essential for exocytosis in many cell types. Syntaxins, located on the terminal plasma membrane (T-SNAREs), are a critical component of the secretosomal complex involved in vesicular docking, fusion, and exocytosis. We analyzed syntaxin 1A mRNA and protein in fetal rat lung ontogeny, demonstrating peak expression on about day 19 of embryonic development, immediately preceding type II pneumocyte differentiation. Syntaxin 1A is predominantly expressed by lipofibroblasts, which are required for bombesin-like peptide-induced surfactant phospholipid synthesis (choline uptake) by isolated type II cells. In organ cultures, anti-syntaxin 1A antibody HPC-1 blocks choline uptake both at baseline and when induced by bombesin-like peptide or dexamethasone. HPC-1 also promotes thymidine uptake in parallel in a dose-dependent fashion. These observations indicate a potential role for syntaxin 1A during fetal lung development, possibly through involvement in secretion of mesenchymal cell-derived factors that induce terminal type II cell differentiation.

Diethylstilbestrol-induced perinatal lethality in the rat. II. Perturbation of parturition.

Evidence is presented suggesting that the fetolethal properties of diethylstilbestrol (DES) are indirect, mediated maternally through a perturbation of the normal mechanisms of parturition. Oral administration of the compound to Sprague-Dawley rats near Day 18 of pregnancy was shown to delay the onset of parturition, prolong labor, and induce dystocia, with a concomitant large increase in perinatal mortality. Exposure during Days 8-16 was without effect, whereas treatment in the Day 18-20 interval resulted in preterm delivery. Inability to initiate labor at term, accompanied by fetal death, also resulted from the administration of hCG on Days 16-18. The relative incidence of stillbirths in DES-exposed pups was markedly decreased by Caesarean delivery. The average weight of the maternal pituitary gland was not affected by treatment, whereas maternal adrenal glands were 30% larger. Maternal blood levels of corticosterone were not significantly elevated, however. The average number of follicles on Day 21 was significantly reduced by DES, and a histological analysis failed to demonstrate a luteotropic effect of the compound. In dams treated on Days 8-18, serum progesterone was reduced by as much as 60%, and total estrogens were 32% lower than in controls. We conclude that DES acts in the rat to depress the preterm levels of steroid hormones, which leads to a failure of uterine contraction accompanied by placental detachment and fetal death.