论文标题：Prenatal Allergen Exposure Perturbs Sexual Differentiation and Programs Lifelong Changes in Adult Social and Sexual Behavior

期刊：

作者：Kathryn M. Lenz, Lindsay A. Pickett, Christopher L. Wright, Anabel Galan, Margaret M. McCarthy

发表时间：2019/03/18

数字识别码： 10.1038/s41598-019-41258-2

原文链接：

性别分化是大脑为男性或女性的典型行为做好准备的早期明升m88过程。这一过程由性染色体、激素和明升m88早期经历主导。最近发表在Scientific Reports上的一项新研究Prenatal Allergen Exposure Perturbs Sexual Differentiation and Programs Lifelong Changes in Adult Social and Sexual Behavior发现，雄性大鼠大脑中的先天免疫细胞（包括小胶质细胞和肥大细胞）比雌性更多。

神经免疫细胞也是性别分化过程的关键参与者，专门调控视前区的突触发育，以及形成成年期雄性典型的性行为。而肥大细胞，则因其在过敏反应中的作用而为人所知。因此，在本研究中，作者试图确定雌性在怀孕期间的过敏反应是否会影响其后代视前区的性别分化，进而影响后代在之后生活中的社会性行为。

怀孕大鼠对卵白蛋白（OVA）过敏，在妊娠第15天用OVA进行滴鼻处理，经观测发现其免疫球蛋白E 水平升高，证明它产生了强烈的过敏性炎症。研究人员对这些受过敏原刺激的母鼠后代的一部分与新生早期的大鼠对照组进行比较评估，评估的参数包括大脑内的肥大细胞和小胶质细胞的活力，视前区神经元下游树突棘的形状，或待其成年后比较行为和树突棘差异。

在母体子宫内暴露于过敏性炎症增加了新生大鼠大脑中的肥大细胞和小胶质细胞的活力，并导致雌性视前区中树突棘密度的雄性化。在成年期，与对照组雌性相比，实验组雌性表现出更多的雄性爬跨行为。与此相反，雄性表现出去雄性特征的迹象，包括小胶质细胞的活力降低，新生儿树突棘的密度降低，雄性典型交配行为减少，以及对雌性典型信息的嗅觉偏好降低。这些结果表明，明升m88早期的过敏反应可能通过对脑部肥大细胞的潜在影响，对雄性和雌性的性行为都产生先天性影响。

图1：产前过敏和产后免疫示意图

摘要：Sexual differentiation is the early life process by which the brain is prepared for male or female typical behaviors, and is directed by sex chromosomes, hormones and early life experiences. We have recently found that innate immune cells residing in the brain, including microglia and mast cells, are more numerous in the male than female rat brain. Neuroimmune cells are also key participants in the sexual differentiation process, specifically organizing the synaptic development of the preoptic area and leading to male-typical sexual behavior in adulthood. Mast cells are known for their roles in allergic responses, thus in this study we sought to determine if exposure to an allergic response of the pregnant female in utero would alter the sexual differentiation of the preoptic area of offspring and resulting sociosexual behavior in later life. Pregnant rats were sensitized to ovalbumin (OVA), bred, and challenged intranasally with OVA on gestational day 15, which produced robust allergic inflammation, as measured by elevated immunoglobulin E. Offspring of these challenged mother rats were assessed relative to control rats in the early neonatal period for mast cell and microglia activation within their brains, downstream dendritic spine patterning on POA neurons, or grown to adulthood to assess behavior and dendritic spines. In utero exposure to allergic inflammation increased mast cell and microglia activation in the neonatal brain, and led to masculinization of dendritic spine density in the female POA. In adulthood, OVA-exposed females showed an increase in male-typical mounting behavior relative to control females. In contrast, OVA-exposed males showed evidence of dysmasculinization, including reduced microglia activation, reduced neonatal dendritic spine density, decreased male-typical copulatory behavior, and decreased olfactory preference for female-typical cues. Together these studies show that early life allergic events may contribute to natural variations in both male and female sexual behavior, potentially via underlying effects on brain-resident mast cells.

阅读论文全文请访问：

期刊介绍： () is an online, open access journal from the publishers of Nature. We publish scientifically valid primary research from all areas of the natural and clinical sciences.

The 2017 journal metrics for Scientific Reports are as follows:

•2-year impact factor: 4.122

•5-year impact factor: 4.609

•Immediacy index: 0.576

•Eigenfactor® score: 0.71896

•Article Influence Score: 1.356

•2-year Median: 2

（来源：明升手机版(明升中国)）