Oxidative Stress and Neurodevelopmental Outcomes in Rat Offspring with Intrauterine Growth Restriction Induced by Reduced Uterine Perfusion

Marcelo E Rains,Norma B Ojeda,Colin B Muncie,Yi Pang,Lir-Wan Fan,Lu-Tai Tien

doi:10.3390/brainsci11010078

Abstract

Intrauterine growth restriction (IUGR) is a major cause of morbidity and mortality and is worldwide associated with delayed neurodevelopment. The exact mechanism involved in delayed neurodevelopment associated with IUGR is still unclear. Reduced uterine perfusion (RUP) is among the main causes of placental insufficiency leading to IUGR, which is associated with increases in oxidative stress. This study investigated whether oxidative stress is associated with delayed neurodevelopment in IUGR rat pups. Pregnant rats were exposed to RUP surgery on gestational day 14 to generate IUGR rat offspring. We evaluated offspring’s morphometric at birth, and neurodevelopment on postnatal day 21 (PD21) as well as markers of oxidative stress in plasma and brain. Offspring from dams exposed to RUP showed significant (p < 0.05) lower birth weight compared to controls, indicating IUGR. Motor and cognitive deficits, and levels of oxidative stress markers, were significantly (p < 0.05) elevated in IUGR offspring compared to controls. IUGR offspring showed significant (p < 0.05) negative correlations between brain lipid peroxidation and neurocognitive tests (open field and novel object recognition) in comparison with controls. Our findings suggest that neurodevelopmental delay observed in IUGR rat offspring is associated with increased levels of oxidative stress markers.

Highlights

Intrauterine growth restriction (IUGR) is the term attributed to a fetus that has not reached its full growth potential, as measured by weight, length, and head circumference [1]; it represents a condition considered to have a major negative impact on global neonatal health and outcomes [2]
Effects of Reduced Uterine Perfusion on Offspring’s Body Weight. Both male and female rat offspring exposed to reduced uterine perfusion (RUP) showed significantly lower weight at birth (PD0) (p < 0.0001) and at postnatal day 21 (PD21) (p < 0.0001) compared to offspring exposed to sham surgery (Controls) (Figure 1A,B)
Our results show that the levels of pro-oxidative stress markers, including superoxide anion and NADPH oxidase-dependent superoxide anion, were higher in the plasma samples of IUGR offspring compared to controls (Figure 4), while the levels of anti-oxidative markers, including SOD and total antioxidant capacity, were lower in IUGR rats as compared to their control counterparts (Figure 5)

Summary

Introduction

Intrauterine growth restriction (IUGR) is the term attributed to a fetus that has not reached its full growth potential, as measured by weight, length, and head circumference [1]; it represents a condition considered to have a major negative impact on global neonatal health and outcomes [2]. What has not always been available, is the technology to detect growth-restricted development in utero, and thence to help these neonates reach full growth potential. Such relatively recent technologies as ultrasound, which can measure biparietal diameter, head circumference, abdominal circumference and femur length, have become important tools in the effort to better characterize and address IUGR [4]

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Results

Discussion

Conclusion