PMID- 37333114
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231129
DP  - 2023 Jun 7
TI  - Sex and age differences in social and cognitive function in offspring exposed to 
      late gestational hypoxia.
LID - rs.3.rs-2507737 [pii]
LID - 10.21203/rs.3.rs-2507737/v1 [doi]
AB  - 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.
FAU - Mabry, Steve
AU  - Mabry S
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Wilson, E Nicole
AU  - Wilson EN
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Bradshaw, Jessica L
AU  - Bradshaw JL
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Gardner, Jennifer J
AU  - Gardner JJ
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Fadeyibi, Oluwadarasimi
AU  - Fadeyibi O
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Vera, Edward Jr
AU  - Vera E Jr
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Osikoya, Oluwatobiloba
AU  - Osikoya O
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Cushen, Spencer C
AU  - Cushen SC
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Karamichos, Dimitrios
AU  - Karamichos D
AD  - UNTHSC: University of North Texas Health Science Center.
FAU - Goulopoulou, Styliani
AU  - Goulopoulou S
AD  - Loma Linda University School of Medicine.
FAU - Cunningham, Rebecca L
AU  - Cunningham RL
AUID- ORCID: 0000-0001-5984-5516
AD  - UNT Health Science Center: University of North Texas Health Science Center.
LA  - eng
GR  - R01 HL146562/HL/NHLBI NIH HHS/United States
GR  - R01 NS091359/NS/NINDS NIH HHS/United States
GR  - R25 HL125447/HL/NHLBI NIH HHS/United States
GR  - T32 AG020494/AG/NIA NIH HHS/United States
PT  - Preprint
DEP - 20230607
PL  - United States
TA  - Res Sq
JT  - Research square
JID - 101768035
UIN - Biol Sex Differ. 2023 Nov 11;14(1):81. PMID: 37951901
PMC - PMC10275064
OTO - NOTNLM
OT  - Morris water maze
OT  - autism spectrum disorder
OT  - chronic intermittent hypoxia
OT  - hippocampus
OT  - marble burying behaviors
OT  - open field
OT  - prenatal programming
OT  - sex differences
OT  - social behaviors
COIS- Competing interests: The authors declare that they have no competing interests.
EDAT- 2023/06/19 06:42
MHDA- 2023/06/19 06:43
PMCR- 2023/06/16
CRDT- 2023/06/19 02:46
PHST- 2023/06/19 06:42 [pubmed]
PHST- 2023/06/19 06:43 [medline]
PHST- 2023/06/19 02:46 [entrez]
PHST- 2023/06/16 00:00 [pmc-release]
AID - rs.3.rs-2507737 [pii]
AID - 10.21203/rs.3.rs-2507737/v1 [doi]
PST - epublish
SO  - Res Sq [Preprint]. 2023 Jun 7:rs.3.rs-2507737. doi: 10.21203/rs.3.rs-2507737/v1.