Prenatal Hypoxic Insults Impact Brain Vulnerability

Abstract

Maternal hypoxic insults during gestation may lead to an increased risk for neurodegenerative diseases, such as Parkinson's disease (PD), in progeny. Maternal hypoxic stress is a common consequence of many late-stage prenatal stressors (e.g., preeclampsia, eclampsia, inflammation, placental abruption). It is unknown whether maternal hypoxic insults during late gestation have long-term effects on brain regions associated with PD, such as the nigrostriatal pathway. We hypothesized that late gestational maternal hypoxia would result in sustained nigrostriatal impairment in male progeny. To determine whether late-stage gestational hypoxia exposure induced PD-associated behaviors and oxidative stress in progeny, timed pregnant Long-Evans rats were exposed to five days (gestational days: 15-19) of chronic intermittent hypoxia (CIH) or room air normoxia. Progeny were tested during two developmental stages (pubertal and young adult) as late-stage gestational insults can impair the neuronal organization of the brain, which can impact pubertal and young adult functions. To examine PD-associated behavioral phenotype of motor dysfunction, we quantified fine and gross motor behaviors in an open field arena. To examine the integrity of the nigrostriatal pathway, we quantified ultrasonic vocalizations. Our results showed that maternal CIH during late gestation did not impact gross or fine motor behaviors nor circulating oxidative stress. However, maternal CIH during late gestation did impair the nigrostriatal pathway integrity during puberty and young adulthood in both male and female progeny. Long-lasting consequences of maternal CIH during late gestation was most evident in young adult male progeny. Overall, we conclude that maternal hypoxia during late gestation induced sustained nigrostriatal pathway impairment in males more than females, which may underlie the increased risk for PD in men compared to women.