Date Published: April 19, 2019
Publisher: Public Library of Science
Author(s): Reza Khazaee, Lynda A. McCaig, Cory Yamashita, Daniel B. Hardy, Ruud A. W. Veldhuizen, Nick Ashton.
Limited information is available on how fetal growth retardation (FGR) affects the lung in the neonatal period in males and females. This led us to test the hypothesis that FGR alters lung mechanics and the surfactant system during the neonatal period. To test this hypothesis a model of FGR was utilized in which pregnant rat dams were fed a low protein diet during both the gestation and lactation period. We subsequently analyzed lung mechanics using a FlexiVent ventilator in male and female pups at postnatal day 7 and 21. Lung lavage material was obtained at postnatal day 1, 7 and 21, and was used for analysis of the surfactant system which included measurement of the pool size of surfactant and its subfraction as well as the surface tension reducing ability of the surfactant. The main result of the study was a significantly lower lung compliance and higher tissue elastance which was observed in FGR female offspring at day 21 compared to control offspring. In addition, female LP offspring exhibited lower surfactant pool sizes at postnatal day 1compared to controls. These changes were not observed in the male offspring. It is concluded that FGR has a different impact on pulmonary function and on surfactant in female, as compared to male, offspring.
Epidemiological studies provide strong evidence for the negative impact of fetal growth restriction (FGR) on numerous short and long-term health outcomes of the offspring . Defined as an infant with a birthweight below the 10th percentile for its gestational age, FGR has been shown to contribute to altered neurodevelopment and impaired growth in the immediate neonatal period, as well as chronic diseases such as diabetes, hypertension, and dyslipidemia later in life [2,3]. Both human epidemiological studies and animal models suggest many of these adverse postnatal outcomes can be sex-specific [4–6]. With respect to the lung, FGR has been implicated in poor pulmonary health; for example it has been suggested to be a risk factor for the development of asthma .
The bodyweight of the offspring at day 1, 7 and 21 is shown in Table 1. The data indicates lower bodyweight in the low protein diet group compared to the control diet animals in both female and male offspring. This difference was significant at both day 1 and 21. The percent difference (~35%) in body weight at Day 21 was the same between male and female offspring.
This study tested the hypothesis that FGR induced by maternal protein restriction during perinatal life alters lung mechanics and the surfactant system. The results supported this hypothesis with regards to lung mechanics as significantly lower lung compliance, higher tissue elastance and higher airway resistance were observed in LP female offspring at day 21. In addition, female LP offspring exhibited lower surfactant pool sizes at day 1, which was not observed in the male offspring. No differences in surfactant pools on other postnatal days were observed and surfactant biophysical properties were not significantly different among groups at any of the timepoints. Collectively, this data suggests that FGR has a different impact on pulmonary function in female, as compared to male, offspring. It also indicates that the significant alterations to lung compliance at day 21 in female offspring occurs in the absence of alterations to the pulmonary surfactant system.