Stimulasi, Deteksi dan Intervensi Dini Orang Tua terhadap Pencegahan Penyimpangan Pertumbuhan dan Perkembangan Anak Balita

Abstract

INTRODUCTION: Intrauterine growth restriction (IUGR) is a leading cause of fetal morbidity and mortality linked to cardiovascular disease later in life. Maternal hypoxia can lead to placental oxidative stress mainly derived from the mitochondria, which is associated with IUGR and abnormal fetal cardiomyocyte development. We hypothesized that maternal MitoQ, a mitochondrial antioxidant, treatment would prevent IUGR and abnormal development of fetal cardiomyocytes. METHODS: Pregnant rats were randomly injected with MitoQ loaded nanoparticles (125 μM) or saline via tail vein on gestational day (GD) 15 (nanoparticles were used to restrict treatment to the placenta and prevent its passage to the fetus). Rats were further subdivided into two groups exposed to either hypoxia (11% O2) or normoxia (21% O2) from GD 15-21 (term; 22 days). On GD 21, pregnant dams were sacrificed and pups were separated into males and females. Offspring body and heart weights were assessed. Placental oxidative stress was measured by performing DCF (dichlorofluorescein) staining. Area and binucleation of fixed cardiomyocytes were assessed. RESULTS: In male and female offspring, hypoxia led to IUGR, increased cardiac hypertrophy and placental oxidative stress (normoxia: 2.27±1.55 vs. hypoxia: 13.34±3.96 arbitrary units (a.u.), P<0.05). MitoQ treatment prevented oxidative stress (hypoxia+MitoQ: 2.48±1.06 a.u.), normalized the heart weight in both sexes and prevented IUGR in female fetuses. In male fetuses only, relative cardiomyocyte area (normalized to heart weight) was significantly increased in the hypoxic group (normoxia: 0.019±0.002 mm2/g vs. hypoxia: 0.026±0.002 mm2/g, P<0.05) and MitoQ treatment prevented this (hypoxia+MitoQ: 0.017±0.002 mm2/g). No differences in the percentage of binucleated cardiomyocytes were observed. CONCLUSIONS: We observed sex-specific effects of hypoxia and MitoQ treatment on fetal growth and cardiomyocyte development. Preventing placental oxidative stress using MitoQ may be a novel approach to improve fetal growth and attenuate cardiomyocyte hypertrophy in IUGR offspring.