Early life adversity (ELA) increases risk for negative health outcomes, with sex disparities in prevalence and form of ELA experienced and risk for neuropsychiatric pathology. ELA comes in many forms (e.g. parental neglect/loss, limited access to resources) but whether disparate forms of ELA have common effects on outcomes, and if males and females are equally affected, remains unknown. Epidemiological studies often fail to accurately account for differences in type, timing, and duration of adversity experienced. Rodent models allow precise control of many of these variables. However, differences in the form of ELA, and species, strain, housing, and testing paradigms used, may contribute to differences in outcomes leading to questions of whether differences are the result of the form of ELA or these other variables. Here, we directly compared two mouse models of ELA, maternal separation (MS) and limited bedding (LB) in males and females on development of the body, motor and visual milestones, stress physiology, and anxiety-like behavior. LB affected timing of early milestones, somatic growth, and stress physiology in both sexes, yet only females showed later anxiety-like behaviors. MS rearing affected males and females similarly in early milestone development, yet only males showed changes in stress physiology and anxiety-like outcomes. These studies provide a platform to directly compare MS and LB models within one lab. The current work advances our understanding of the unique features of ELA that shape early neurodevelopmental events and risk for later pathology, increasing the translational relevance of these ELA models.

中文翻译：

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早期生活逆境的类型对小鼠的早期成熟里程碑产生不同的、性别依赖性的影响。

早年逆境 (ELA) 会增加负面健康结果的风险，其中 ELA 患病率和形式存在性别差异，并且会增加神经精神病理学风险。ELA 有多种形式（例如父母的忽视/丧失、获得资源的机会有限），但不同形式的 ELA 是否对结果有共同影响，以及男性和女性是否同样受到影响，仍然未知。流行病学研究常常无法准确解释所经历的逆境的类型、时间和持续时间的差异。啮齿动物模型可以精确控制其中许多变量。然而，ELA 形式以及所使用的物种、菌株、饲养环境和测试范式的差异可能会导致结果差异，从而引发以下问题：差异是 ELA 形式还是这些其他变量的结果。在这里，我们直接比较了雄性和雌性两种 ELA、母体分离 (MS) 和有限床上用品 (LB) 小鼠的身体发育、运动和视觉里程碑、应激生理学和焦虑样行为。LB 会影响两性的早期里程碑、躯体生长和应激生理学的时间，但只有雌性随后表现出类似焦虑的行为。MS 抚养对男性和女性早期里程碑发育的影响相似，但只有男性表现出应激生理和焦虑样结果的变化。这些研究提供了一个在一个实验室内直接比较 MS 和 LB 模型的平台。目前的工作加深了我们对 ELA 独特特征的理解，这些特征塑造了早期神经发育事件和后期病理学的风险，增加了这些 ELA 模型的转化相关性。