孕期母体免疫抑制并不能防止后代出现异常行为。

IF 4.9 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Biology of Sex Differences Pub Date : 2024-03-26 DOI:10.1186/s13293-024-00600-8
Ashley Griffin, Teylor Bowles, Lucia Solis, Teryn Railey, Samer Beauti, Reanna Robinson, Shauna-Kay Spencer, James P Shaffery, Kedra Wallace
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引用次数: 0

摘要

背景:与未受影响的妊娠相比,高血压妊娠的后代患神经发育和神经行为障碍的风险更高。我们利用子痫前期(PreE;妊娠 20 周后新发高血压)和 HELLP(溶血、肝酶升高和血小板低)的啮齿类动物模型,研究了其后代在青春期的行为结果:一部分母体接受了 T 细胞活化抑制剂 Orencia 的治疗,因为 T 细胞与妊娠期高血压和炎症的诱发有关。我们假设高血压母鼠的后代会在社交、认知、运动和焦虑测试中出现不良行为,而接受Orencia治疗的母鼠的后代则会表现出较少的不良行为:PreE+Orencia母鼠(p 60)的雄性后代在前额叶皮层和海马中均有髓鞘碱性蛋白(MBP)和NeuN表达。在海马和前额叶皮质中,无论性别如何,各组的 MBP 或 NeuN 表达量均无差异:本研究结果表明,妊娠期高血压疾病的后代会出现行为变化,特别是认知差异。这项研究表明,后代的神经行为发育存在性别差异,部分原因是受到妊娠高血压疾病类型和母体免疫系统改变的影响。
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Maternal immune suppression during pregnancy does not prevent abnormal behavior in offspring.

Background: Offspring of hypertensive disorders of pregnancy are at an increased risk of developing neurodevelopmental and neurobehavioral disorders compared to offspring from non-affected pregnancies. Using rodent models of Preeclampsia (PreE; new onset of hypertension after 20 weeks gestation) and HELLP (hemolysis, elevated liver enzymes, and low platelets), we studied the behavioral outcome of their offspring in adolescence.

Methods: A subset of dams received Orencia, a T-cell activation inhibitor, as T cells have been associated with the induction of hypertension and inflammation during pregnancy. We hypothesized that offspring from hypertensive dams would experience adverse behavioral outcomes in social, cognitive, locomotor, and anxiety tests, and offspring from dams treated with Orencia would demonstrate less adverse behaviors.

Results: Male offspring of PreE + Orencia dams (p < 0.05) and female offspring from HELLP + Orencia dams (p < 0.05) spent more time playing compared to normal pregnant offspring. All offspring from hypertensive and Orencia-treated dams performed worse on the Barnes Maze test compared to normal pregnant. We also measured adult (postnatal day > 60) myelin basic protein (MBP) and NeuN expression in both the prefrontal cortex and hippocampus. In the hippocampus and prefrontal cortex, there was no difference in expression of either MBP or NeuN in all groups regardless of sex.

Conclusion: The results from this study suggest that offspring of hypertensive disorders of pregnancy have behavioral changes, specifically cognitive differences. This study has shown that there is a sex dependent difference in offspring neurobehavioral development, influenced in part by the type of hypertensive disorder of pregnancy, and alterations in the maternal immune system.

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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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