Abstract
In human and ovine fetuses, glucocorticoids stimulate leptin secretion, although the extent to which leptin mediates the maturational effects of glucocorticoids on pulmonary development is unclear. This study investigated the effects of leptin administration on indices of lung structure and function before birth. Chronically catheterized singleton sheep fetuses were infused iv for 5 days with either saline or recombinant ovine leptin (0.5 mg/kg · d leptin (LEP), 0.5 LEP or 1.0 mg/kg · d, 1.0 LEP) from 125 days of gestation (term ∼145 d). Over the infusion, leptin administration increased plasma leptin, but not cortisol, concentrations. On the fifth day of infusion, 0.5 LEP reduced alveolar wall thickness and increased the volume at closing pressure of the pressure-volume deflation curve, interalveolar septal elastin content, secondary septal crest density, and the mRNA abundance of the leptin receptor (Ob-R) and surfactant protein (SP) B. Neither treatment influenced static lung compliance, maximal lung volume at 40 cmH2O, lung compartment volumes, alveolar surface area, pulmonary glycogen, protein content of the long form signaling Ob-Rb or phosphorylated signal transducers and activators of transcription-3, or mRNA levels of SP-A, C, or D, elastin, vascular endothelial growth factor-A, the vascular endothelial growth factor receptor 2, angiotensin-converting enzyme, peroxisome proliferator-activated receptor γ, or parathyroid hormone-related peptide. Leptin administration in the ovine fetus during late gestation promotes aspects of lung maturation, including up-regulation of SP-B.
Highlights
In human and ovine fetuses, glucocorticoids stimulate leptin secretion, the extent to which leptin mediates the maturational effects of glucocorticoids on pulmonary development is unclear
The rise in pulmonary angiotensin-converting enzyme (ACE) concentration induced by glucocorticoids in fetal sheep near term depends on an intact thyroid gland and up-regulation of thyroid hormone activity [8]
Stereological analyses After 2 weeks in fixative, a 1.0 ϫ 1.0 ϫ 0.5-cm cuboid was cut from the inflated lung lobe; the volume was determined by water displacement, and the tissue was embedded in paraffin wax for morphometric analysis
Summary
Animals Thirty pregnant Welsh Mountain ewes of known gestational age and carrying singleton fetuses were housed in individual pens and fed concentrates (200 g/d; 18% protein and 10 MJ/kg; Sheep Nuts 6; H&G Beart) with hay, water, and a mineral block ad libitum. Surgical procedures The pregnant ewes were fasted for 18 –24 hours before surgery but had free access to water. At between 118 and 120 days of pregnancy (term ϳ145 d), the ewes were anesthetized with halothane (1.5–2.0% in O2-N2O) and positive pressure ventilation. All fetuses were administered with 100-mg ampicillin iv (Penbritin, Beecham Animal Health) and 2-mg gentamycin iv (Frangen-100; Biovet). The ewes were administered with antibiotics im (procaine penicillin, Depocillin, Mycofarm) on the day of surgery and for 3 days thereafter
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