Related Experiment Video
Updated: Aug 27, 2025
A Rat Model of Mild Intrauterine Hypoperfusion with Microcoil Stenosis
Published on: January 7, 2018
Gestational hypoxia in late pregnancy differentially programs subcortical brain maturation in male and female rat
E Nicole Wilson1, Steve Mabry1, Jessica L Bradshaw1
1Department of Pharmaceutical Sciences, UNT System College of Pharmacy, School of Pharmacy, University of North Texas Health Science Center, 3500 Camp Bowie Boulevard, Fort Worth, TX, 76107, USA.
Insights
Gestational hypoxia during late pregnancy impacts offspring brain development, specifically the nigrostriatal pathway. This prenatal stress causes long-term, sex-dependent changes in brain maturation, potentially increasing neuropsychiatric disorder risk.
Area of Science:
- Neuroscience
- Developmental Biology
- Obstetrics
Background:
- Hypoxia during pregnancy is linked to complications like preeclampsia.
- In utero hypoxic stress can affect fetal brain maturation, particularly subcortical pathways.
- Long-term effects of late-gestation hypoxia on offspring brain development remain unclear.
Purpose of the Study:
- To investigate the impact of late-gestation hypoxia on the developmental programming of subcortical brain maturation.
- To focus on the effects on the nigrostriatal pathway in offspring.
Main Methods:
- Timed pregnant Long-Evans rats were exposed to hypoxia from gestational day 15-19.
- Offspring (male and female) were assessed during puberty and young adulthood.
- Nigrostriatal pathway maturation was evaluated via behavior (locomotion, ultrasonic vocalizations) and neuroanatomy.
Main Results:
- Gestational hypoxia adversely affected nigrostriatal pathway refinement in an age- and sex-dependent manner.
- Pubertal females showed decreased ultrasonic vocalization (USV) frequency and duration.
- Adult males exhibited altered USV latency, intensity, and bandwidth; no structural changes were observed.
Conclusions:
- Prenatal hypoxia exposure mediates developmental programming of brain pathways.
- Male offspring showed more long-term adverse effects on nigrostriatal pathway refinement compared to females.
- Impaired pathway maturation may elevate the risk for neuropsychiatric disorders.
Background:
Hypoxia is associated with pregnancy complications, such as preeclampsia, placental abruption, and gestational sleep apnea. Hypoxic insults during gestation can impact the brain maturation of cortical and subcortical pathways, such as the nigrostriatal pathway. However, the long-term effects of in utero hypoxic stress exposure on brain maturation in offspring are unclear, especially exposure during late gestation. The purpose of this study was to determine the impact of gestational hypoxia in late pregnancy on developmental programming of subcortical brain maturation by focusing on the nigrostriatal pathway.
Methods:
Timed pregnant Long-Evans rats were exposed to chronic intermittent hypoxia or room air normoxia from gestational day (GD) 15-19 (term 22-23 days). Male and female offspring were assessed during two critical periods: puberty from postnatal day (PND) 40-45 or young adulthood (PND 60-65). Brain maturation was quantified by examining (1) the structural development of the nigrostriatal pathway via analysis of locomotor behaviors and the substantia nigra dopaminergic neuronal cell bodies and (2) the refinement of the nigrostriatal pathway by quantifying ultrasonic vocalizations (USVs).
Results:
The major findings of this study are gestational hypoxia has age- and sex-dependent effects on subcortical brain maturation in offspring by adversely impacting the refinement of the nigrostriatal pathway in the absence of any effects on the structural development of the pathway. During puberty, female offspring were impacted more than male offspring, as evidenced by decreased USV call frequency, chirp USV call duration, and simple call frequency. In contrast, male offspring were impacted more than female offspring during young adulthood, as evidenced by increased latency to first USV, decreased simple USV call intensity, and increased harmonic USV call bandwidth. No effects of gestational hypoxia on the structural development of the nigrostriatal pathway were observed.
Conclusions:
These novel findings demonstrate hypoxic insults during pregnancy mediate developmental programming of the cortical and subcortical pathways, in which male offspring exhibit long-term adverse effects compared to female offspring. Impairment of cortical and subcortical pathways maturation, such as the nigrostriatal pathway, may increase risk for neuropsychiatric disorders (e.g., mood disorders, cognitive dysfunction, brain connectivity dysfunction).
