AbstractsBiology & Animal Science

An investigation of the basis for the male disadvantage in respiratory function and survival following preterm birth

by Noreen Ishak

Institution: Monash University
Department: Department of Anatomy and Developmental Biology
Year: 2015
Keywords: Physiology; Respiration; Lung; Preterm birth
Record ID: 1071398
Full text PDF: http://arrow.monash.edu.au/hdl/1959.1/1162150


Preterm birth accounts for about 8–12% of live births in most developed countries. It is widely known that male preterm infants have a greater risk of respiratory insufficiency than females, which may have long-term consequences. Male preterm infants require more initial respiratory and circulatory support than preterm females. To date, little is known about the causes and basis of this male disadvantage and further investigation is required for a better understanding. The aim of this study was to make an in-depth investigation of the possible causes for the male disadvantage in respiratory function following preterm birth. In one study (fetal study group) we used fetal sheep at 131 days of gestation (d GA; term is 147 days) to provide lung tissue for morphometric analysis and measurement of gene expression of surfactant proteins and tropoelastin in male and female preterm fetuses. In two other groups of sheep (postnatal studies) we used an established model of moderate preterm birth for physiological studies before and after preterm birth. In the postnatal studies, preterm lambs were delivered at 133d GA as lambs born at this age demonstrate lower survival in males than females. The animals in the postnatal study group were grouped into two cohorts; one group was studied for 4 hours (h) after birth and the other group was studied for 8 h to determine whether any differences between the sexes changed with time after birth. Pregnant ewes from both cohorts underwent surgery to chronically implant fetuses with catheters at ~125d GA for the measurement of fetal physiological status at 131 and 132d GA and fluid (plasma, lung liquid and amniotic fluid) sampling and collection from 125–133d GA. A small dose of betamethasone (5.7 mg of Celestone Chronodose) was administered to the ewe at 131d GA. Unanaesthetised lambs were delivered at 133d GA, approximately 14 days before term, and then studied physiologically for 4 h or 8 h after delivery. At the end of the 4 h or 8 h study periods, the lambs were euthanised for measurement of static lung compliance and collection of bronchoalveolar lavage fluid (BALF) and lung tissue. The surfactant phospholipid composition and protein concentration of BALF and the gene expression of surfactant proteins (SP)-A, -B, -C and -D and the protein expression of SP-A and pro-SP-C in lung tissue were also measured. We observed that, at necropsy, lungs excised from fetal sheep at 131d GA were similar in males and females in terms of lung morphology and surfactant protein and tropoelastin gene expression. Our findings indicate that these factors did not contribute to the male disadvantage. Minor differences in surfactant phospholipid composition were observed in the fetal lung liquid collected but it is unknown to what extent they affect respiratory outcome. In the postnatal study where lambs were monitored for 4 h following preterm birth, male lambs demonstrated poorer arterial blood gas parameters (lower pH and higher PaCO₂,) higher arterial glucose and lactate concentrations and had a greater…