妊娠晚期缺氧暴露的后代社会和认知功能的性别和年龄差异。

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2023-11-11 DOI:10.1186/s13293-023-00557-0
Steve Mabry, E Nicole Wilson, Jessica L Bradshaw, Jennifer J Gardner, Oluwadarasimi Fadeyibi, Edward Vera, Oluwatobiloba Osikoya, Spencer C Cushen, Dimitrios Karamichos, Styliani Goulopoulou, Rebecca L Cunningham
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引用次数: 0

摘要

背景:妊娠期睡眠呼吸暂停是一种缺氧睡眠障碍,影响8-26%的妊娠,并增加后代中枢神经系统功能障碍的风险。具体来说,胎儿海马对缺氧损伤的敏感性存在性别差异,海马损伤与社交功能障碍、重复行为、焦虑和认知障碍有关。然而,尚不清楚妊娠期睡眠呼吸暂停是否会影响这些海马相关功能,以及性别和年龄是否会改变这些影响。为了研究妊娠期睡眠呼吸暂停与海马相关行为之间的关系,我们采用慢性间歇缺氧(CIH)对妊娠晚期睡眠呼吸暂停大鼠进行建模。我们假设妊娠晚期CIH会在后代中产生性别和年龄特异性的社交、焦虑样、重复性和认知障碍。方法:定时妊娠的Long-Evans大鼠从妊娠第15 ~ 19天开始暴露于CIH或室内常氧环境。后代的行为测试发生在青春期或青年期。为了研究妊娠缺氧诱导的行为表型,我们量化了海马相关行为(社交功能、重复行为、焦虑样行为、空间记忆和学习)、海马神经元活动(谷氨酸能NMDA受体、多巴胺转运体、单胺氧化酶-a、早期生长反应蛋白1和双皮质素)和后代循环激素。结果:妊娠晚期CIH诱导后代社会、重复和记忆功能的性别和年龄特异性差异。在女性青春期的后代中,CIH损害了社会功能,增加了重复行为,升高了循环皮质酮水平,但不影响记忆。相比之下,CIH短暂地诱导青春期雄性后代的空间记忆功能障碍,但不影响社交或重复功能。妊娠期CIH对社会行为的长期影响仅在雌性后代中观察到,其中CIH诱导社会脱离,并在成年早期抑制循环皮质酮水平。没有观察到妊娠期CIH对焦虑样行为、海马神经元活动或循环睾酮和雌二醇水平的影响,与后代的性别和年龄无关。结论:我们的研究结果表明,妊娠后期与缺氧相关的妊娠并发症会增加后代行为和生理结局的风险,如社交功能障碍、重复行为和认知障碍,这些风险与性别和年龄有关。
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Sex and age differences in social and cognitive function in offspring exposed to late gestational hypoxia.

Background: Gestational sleep apnea is a hypoxic sleep disorder that affects 8-26% of pregnancies and increases the risk for central nervous system dysfunction in offspring. Specifically, there are sex differences in the sensitivity of the fetal hippocampus to hypoxic insults, and hippocampal impairments are associated with social dysfunction, repetitive behaviors, anxiety, and cognitive impairment. Yet, it is unclear whether gestational sleep apnea impacts these hippocampal-associated functions and if sex and age modify these effects. To examine the relationship between gestational sleep apnea and hippocampal-associated behaviors, we used chronic intermittent hypoxia (CIH) to model late gestational sleep apnea in pregnant rats. We hypothesized that late gestational CIH would produce sex- and age-specific social, anxiety-like, repetitive, 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 gestational hypoxia-induced behavioral phenotypes, we quantified hippocampal-associated behaviors (social function, repetitive behaviors, anxiety-like behaviors, and spatial memory and learning), hippocampal neuronal activity (glutamatergic NMDA receptors, dopamine transporter, monoamine oxidase-A, early growth response protein 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. In female pubertal offspring, CIH impaired social function, increased repetitive behaviors, and elevated 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 on social behaviors 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 in anxiety-like behaviors, hippocampal neuronal activity, or circulating testosterone and 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 behavioral and physiological outcomes in offspring, such as social dysfunction, repetitive behaviors, and cognitive impairment, that are dependent on sex and age.

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来源期刊
Biology of Sex Differences
Biology of Sex Differences ENDOCRINOLOGY & METABOLISM-GENETICS & HEREDITY
CiteScore
12.10
自引率
1.30%
发文量
69
审稿时长
14 weeks
期刊介绍: Biology of Sex Differences is a unique scientific journal focusing on sex differences in physiology, behavior, and disease from molecular to phenotypic levels, incorporating both basic and clinical research. The journal aims to enhance understanding of basic principles and facilitate the development of therapeutic and diagnostic tools specific to sex differences. As an open-access journal, it is the official publication of the Organization for the Study of Sex Differences and co-published by the Society for Women's Health Research. Topical areas include, but are not limited to sex differences in: genomics; the microbiome; epigenetics; molecular and cell biology; tissue biology; physiology; interaction of tissue systems, in any system including adipose, behavioral, cardiovascular, immune, muscular, neural, renal, and skeletal; clinical studies bearing on sex differences in disease or response to therapy.
期刊最新文献
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