Surfactant Content and Type II Cell Development in Fetal Guinea Pig Lungs during Prenatal Starvation

Abstract

ABSTRACT. Prenatal caloric restriction in guinea pigs causes intrauterine growth retardation and reduced neonatal viability and surfactant phosopholipid (PL). We report here fetal surfactant levels in this model, and correlate total lung PL with ultrastructural maturation of surfactant type I1 cells and lamellar bodies (LB). Pregnant guinea pigs were fed ad libitum throughout their 68-d gestation (control), or fed 50% rations from d 45 until term (starved). Fetal lungs were examined at d 55, 60, and 65 for PL content and composition, including disaturated phosphatidylcholine (DPC), and compared with neonates for both groups. Lung lobes were analyzed ultrastructurally in d 65 fetuses for the numerical, volume, and surface densities of type I1 cells and the volume densities of LB. Prenatal starvation caused significant intrauterine growth retardation at all ages; body and dry lung weights were reduced on d 65 by 26 and 23%, respectively. By d 55 and thereafter, starvation decreased total lung P L by 43-45% but did not alter P L composition. On d 65, the total lung volumes and relative numbers, surface densities, and volumes of type I1 cells in tissue and the relative volumes of LB within type I1 cells did not differ by caloric regimen. Thus, starved and control fetuses had similar total volumes of LB per lung (13-15 pL), although starved animals had significantly less lung DPC. Although the total volume of LB per lung correlated well with total lung DPC from d 55 through birth in controls, starvation led to a significant departure from this relationship. These results suggest that the concentration of DPC within LB can vary markedly without changing the size and appearance of the LB, or that the reduced amounts of DPC in starved fetuses represent deficiencies of surfactant from non-LB compartments. Supported by Grant HL-37386 from the National Heart, Lung, and Blood institute 28 controls, the lungs of starved rat fetuses appear to have reduced septation and delayed surfactant type I1 cell maturation, including the subjective impression of fewer LB in those cells (5). In newborn guinea pigs, the total lung weight, DNA content, alveolar surface area, compliance, and surfactant content are reduced significantly when pregnant animals receive 50% rations of their normal food during the last 3 wk of their 68-d gestation (4, 6).However, the fetal maturation of alveolar type I1 cells after such malnutrition-induced IUGR has never been accurately quantitated in any of these animal models.There are few data on the cellularity of normal human fetal lungs, and none for human hypoplastic lungs caused by or associated with any form of IUGR or prematurity (7). This is despite a mortality rate in neonates weighing ~2 5 0 0 g that is 40 times that of larger neonates during the 1st postnatal month, and that smaller neonates show a higher incidence of neonatal respiratory distress (8,9). Thus, animal models of IUGR may improve current understanding of the pulmonary consequences of similar human intrauterine stress. We have asked two...

Effects of Maternal Undernutrition During Late Gestation on the Lung Surfactant System and Morphometry in Rats

“…Total saturated phosphatidylcholine contents were lower in IUGR rats' lungs and the value reached statistical significance on postnatal d 1 only. These results are in agreement with the findings of Lechner et al (11,21), who found that prenatal starvation reduces total lung saturated phospholipids in fetal and term guinea pigs at birth. Ryan et al (25) administered LDL intravenously over 3 h to pregnant rats, and found that saturated phosphatidylcholine content is increased in fetal alveolar pretype II cells.…”

“…Maternal undernutrition during late gestation is associated with poor maternal weight gain and reduced fetal body weight in rats (13,21). IUGR caused by placental insufficiency in sheep reveals similar findings (22,23).…”

Effects of maternal food restriction on offspring lung extracellular matrix deposition and long term pulmonary function in an experimental rat model

“…Although the molecular mechanisms underlying this respiratory compromise are not well established, general cellular and molecular effects of IUGR on the developing lung have been described. 4–15 These include an overall reduction in lung weight, DNA, and protein content, 4–6 reduced surfactant content and activity, 7–9 impaired maturation of the alveolar type II (ATII) cell, 10 decreased alveolar formation, 11–13,15 reduced alveolar surface area for gas exchange, 11,14 an immature and thicker air-blood barrier, and a thicker alveolar wall. 10,14 …”

Effect of Acute Glucose Depletion Following Glucose Excess on Surfactant Phospholipid Synthesis in Developing Fetal Lung

“…The infant of the poorly controlled diabetic mother has a higher incidence of respiratory distress syndrome [ 5,11] , and high insulin and glucose levels have both been found to inhibit fetal lung maturation in various experimental systems [5][6][7][8][9][10] . Maternal starvation also has been reported to result in decreased pulmonary surfactant content in fetal guinea pigs [ 26] .…”