Differential release of prostaglandins by organ cultures of human fetal trachea and lung

Abstract

Human fetal lung at 16-19 weeks gestation has a partially differentiated epithelium, and in organ culture, distal airsacs dilate and the epithelium autodifferentiates to type I and II pneumatocytes, processes regulated by endogenous prostaglandin PGE2. Human fetal trachea, at the same gestation, has a terminally differentiated mucociliary epithelium but after 4-6 d in organ culture, develops squamous metaplasia. Tracheal cultures restricted to 3 d have normal phase-contrast and light microscopy appearances and immunohistochemical reactivities (epithelium: cytokeratin 7,8,18; glutathione S-transferase pi-isozyme; epithelial membrane antigen and mesenchyme; desmin; vimentin). In human fetal trachea organ cultures, the predominant prostaglandins released are 6-keto-PGF1 alpha, PGF2 alpha, and PGE2, a pattern similar to that previously described for human adult trachea and lung. In fetal lung cultures, 13,14-dihydro-15-keto-PGF2 alpha is the major prostaglandin released with lesser amounts of 13,14-dihydro-15-keto-PFG2 alpha,PGF2 alpha,PGE2, and 6-keto-PGF1 alpha. Human fetal lung in vitro has the competence to self-differentiate, as early as 12 weeks gestation and presence of high levels in fetal lung of the inactive metabolite 13,14-dihydro-15-keto-PGE2 relative to PGE2 suggests that active prostaglandin catabolism may be one of the mechanisms to retard this stage of maturation in vivo by limiting PGE2 availability. Surprisingly, the profile of prostaglandins released from fetal lung organ culture does not change to that of a mature lung with terminal differentiation of the epithelium, and this may indicate differences in the expression of key prostaglandin-metabolizing enzymes in developing human fetal lung in culture and with in utero ontogeny.

Regulation of prostaglandin availability in human fetal lung by differential localisation of prostaglandin H synthase-1 and prostaglandin dehydrogenase

“…In contrast, the terminal airway epithelium of human fetal lung in vitro has the competence from 12 weeks gestation to self-differentiate into type I and II pneumatocytes with dilatation of airways equivalent to the volume of a 27-to 30-weekgestation lung (for review, see Conner et al 1998). These above observations support the hypothesis that this phase of terminal airway maturation may be actively retarded in utero, contrasting with other foregut endoderm derivatives where terminal epithelial differentiation occurs much earlier in gestation including the tracheobronchial system (Hume et al 1996b).…”

“…In addition restriction of the bioavailability of hormones by sulphation, for example, of oestrogens (Jones et al 1992) and thyroid hormones (Richard et al 2001), which decreases with gestation, are yet further means to restrict early lung development. In contrast, a gestationally dependent delay in the sulphation and inactivation of androgens, known to delay lung maturation, has been suggested as an additional mechanism retarding terminal epithelial differentiation in human fetal lung (Hume et al 1996b).…”