Impact of intrauterine hypoxia on adolescent and adult cognitive function in rat offspring: sexual differences and the effects of spermidine intervention

Mao, Meng; Yang, Lin; Jin, Zhuo; Li, Ling-Xu; Wang, Yanru; Li, Tingting; Zhao, Yajun; Ai, Jing

doi:10.1038/s41401-020-0437-z

Cited by 13 publications

(5 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, there were differences between these prior studies and our current study, in which sustained hypoxia impaired cognitive function in young adult female offspring [114], decreased repetitive behaviors in young adult male offspring [76,111], and increased anxiety-like behaviors in young adult male offspring [76,111], indicating that the type of hypoxic exposure during this critical period of brain development is important.…”

Section: Discussioncontrasting

confidence: 92%

“…have found equivocal ndings that range from social impairments in male offspring with no effects in female offspring [109,110] to social impairments in female offspring with no effects in male offspring [76,111] or social impairments in both sexes [112]. Reports of sex differences in cognition due to gestational hypoxia have been observed, with impairment observed in male offspring [109,113], female offspring [114], or neither sex [76,112,115]. These behavioral differences in offspring exposed to gestational hypoxia may be due to the timing or the type of hypoxic insult, as they ranged in hypoxia exposure duration (1-21 days), hypoxia cycles (intermittent, sustained hypoxia), and intensity of lowered oxygen concentration (13%-5%).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia

Mabry

Wilson

Bradshaw

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Gestational sleep apnea affects 8-26% of pregnancies and can increase the risk for autism spectrum disorder (ASD) in offspring. ASD is a neurodevelopmental disorder associated with social dysfunction, repetitive behaviors, anxiety, and cognitive impairment. To examine the relationship between gestational sleep apnea and ASD-associated behaviors, we used a chronic intermittent hypoxia (CIH) protocol between gestational days (GD) 15-19 in pregnant rats to model late gestational sleep apnea. We hypothesized that late gestational CIH would produce sex- and age-specific social, mood, and cognitive impairments in offspring. Methods: Timed pregnant Long-Evans rats were exposed to CIH or room air normoxia from GD 15-19. Behavioral testing of offspring occurred during either puberty or young adulthood. To examine ASD-associated phenotypes, we quantified ASD-associated behaviors (social function, repetitive behaviors, anxiety-like behaviors, and spatial memory and learning), hippocampal activity (glutamatergic NMDA receptors, dopamine transporter, monoamine oxidase-A, EGR-1, and doublecortin), and circulating hormones in offspring. Results: Late gestational CIH induced sex- and age-specific differences in social, repetitive and memory functions in offspring. These effects were mostly transient and present during puberty. In female pubertal offspring, CIH impaired social function, increased repetitive behaviors, and increased circulating corticosterone levels, but did not impact memory. In contrast, CIH transiently induced spatial memory dysfunction in pubertal male offspring but did not impact social or repetitive functions. Long-term effects of gestational CIH were only observed in female offspring, wherein CIH induced social disengagement and suppression of circulating corticosterone levels in young adulthood. No effects of gestational CIH were observed on anxiety-like behaviors, hippocampal activity, circulating testosterone levels, or circulating estradiol levels, regardless of sex or age of offspring. Conclusions: Our results indicate that hypoxia-associated pregnancy complications during late gestation can increase the risk for ASD-associated behavioral and physiological outcomes, such as pubertal social dysfunction, corticosterone dysregulation, and memory impairments.

show abstract

Section: Discussioncontrasting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia

Mabry

Wilson

Bradshaw

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…Supplementation with 10 mg/kg/d of SPD reversed age-related cardiac deterioration in rats ( 36 ). More importantly, the mother was an intervention with 5 mg/kg/d of SPD during late pregnancy to improve IUH-induced cognitive and neural function decline ( 51 ) and heart oxidative stress damage in rat offspring ( 32 ). Accordingly, we used the same dose of SPD (5 mg/kg/d) for the pregnant rat exposed to IUH as in our previous study.…”

Section: Discussionmentioning

confidence: 99%

“…mg/kg/d of SPD during late pregnancy to improve IUHinduced cognitive and neural function decline(51) and heart oxidative stress damage in rat offspring(32). Accordingly, we used the same dose of SPD (5 mg/kg/d) for the pregnant rat exposed to IUH as in our previous study.…”

mentioning

confidence: 99%

Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control

et al. 2023

View full text Add to dashboard Cite

Background: Intrauterine hypoxia (IUH) increases the risk of cardiovascular diseases in offspring. As a reactive oxygen species (ROS) scavenger, polyamine spermidine (SPD) is essential for embryonic and fetal survival and growth. However, further studies on the SPD protection and mechanisms for IUH-induced heart damage in offspring are required. Objectives: This study aimed to investigate the preventive effects of prenatal SPD treatment on IUH-induced heart damage in newborn offspring rats and its underlying mitochondrial-related mechanism. Methods: The rat model of IUH was established by exposure to 10% O2 seven days before term. Meanwhile, for seven days, the pregnant rats were given SPD (5 mg.kg-1.d-1; ip). The one-day offspring rats were sacrificed to assess several parameters, including growth development, heart damage, cardiomyocytes proliferation, myocardial oxidative stress, cell apoptosis, and mitochondrial function, and have mitochondrial quality control (MQC), including mitophagy, mitochondrial biogenesis, and mitochondrial fusion/fission. In in vitro experiments, primary cardiomyocytes were subjected to hypoxia with or without SPD for 24 hours. Results: IUH decreased body weight, heart weight, cardiac Ki67 expression, the activity of SOD, and the CAT and adenosine 5'-triphosphate (ATP) levels and increased the BAX/BCL2 expression, and TUNEL-positive nuclei numbers. Furthermore, IUH also caused mitochondrial structure abnormality, dysfunction, and decreased mitophagy (decreased number of mitophagosomes), declined mitochondrial biogenesis (decreased expression of SIRT-1, PGC-1α, NRF-2, and TFAM), and led to fission/fusion imbalance (increased percentage of mitochondrial fragments, increased DRP1 expression, and decreased MFN2 expression) in the myocardium. Surprisingly, SPD treatment normalized the variations in the IUH-induced parameters. Furthermore, SPD also prevented hypoxia-induced ROS accumulation, mitochondrial membrane potential decay, and the mitophagy decrease in cardiomyocytes. Conclusions: Maternal SPD treatment caused IUH-induced heart damage in newborn offspring rats by improving the myocardial mitochondrial function via anti-oxidation and anti-apoptosis, and regulating MQC.

show abstract

“…Notably, sustained late term prenatal hypoxia causes a decrease in cortical spine density [115]. Moreover, subjecting pregnant rat dams to 4 hours of sustained hypoxia (10% oxygen) daily from gestation day 15 to 21 impairs cognition in 2-month-old female, but not male, offspring and actually improves cognition as compared to control offspring at 4 months of age in both males and females [116]. Further, repeated IH during gestation was shown to produce sleep deprivation and fragmentation on the first day of exposure only, with a rebound to normalcy by the second day [117].…”

Section: Plos Biologymentioning

confidence: 99%

Untitled

View full text Add to dashboard Cite

Impact of intrauterine hypoxia on adolescent and adult cognitive function in rat offspring: sexual differences and the effects of spermidine intervention

Cited by 13 publications

References 49 publications

Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia

Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia

Spermidine Alleviates Intrauterine Hypoxia-Induced Offspring Newborn Myocardial Mitochondrial Damage in Rats by Inhibiting Oxidative Stress and Regulating Mitochondrial Quality Control

Untitled

Contact Info

Product

Resources

About