Type of early life adversity confers differential, sex-dependent effects on early maturational milestones in mice.

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, 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.