Early-life adversity disrupts the maturation of neuroendocrine, cognitive, and emotional regulatory systems, yet outcomes likely depend on both the timing of development and sex. Maternal separation (MS) in rodents is a widely used model for studying these effects, yet the sex-specific consequences of distinct postnatal MS windows remain underexplored. Here, we investigated how early postnatal day (P)2–P10, late (P11–P20), or prolonged MS (P2–P20) influences pubertal maturation, spatial memory, and anxiety-like behavior in male and female Sprague–Dawley rats. Pubertal development was assessed through daily visual inspection. Affective behavior was evaluated using dyadic social interaction and light-enhanced startle (LES), and spatial memory was evaluated in the delayed win-shift task during adolescence. Both postnatal timing of adversity exposure and sex influenced the measured outcomes. Females exposed to prolonged or early MS exhibited significantly earlier pubertal initiation, with no effect of MS on pubertal onset in males. Prolonged or early MS exposure also impaired spatial memory, with females affected by prolonged MS and males affected by early MS. Affective measures in males and females were differentially affected by early and late MS exposure. While only late MS exposure yielded more social approach-avoidance behavior in males, females exhibited approach-avoidance changes after both early and late MS. We replicated previous findings that PMS-exposed males display a blunted light-enhanced startle, and now show that late, but not early MS, yields reduced LES in males. Female adolescents, however, responded to early MS with enhanced LES. Together, these findings demonstrate that MS exerts distinct, sex-specific effects on pubertal maturation and behavior depending on the developmental window of adversity. By demonstrating window and sex-dependent effects on pubertal development, anxiety-like behavior, social interaction, and cognition, this work highlights developmental timing and sex as key determinants of early-life stress outcomes and underscores the importance of distinguishing discrete postnatal periods when modeling the consequences of early caregiving disruption. • Early and prolonged maternal separation accelerates pubertal onset in females • Maternal separation impacts startle modulation in a window- and sex-specific fashion • Social behavior and spatial memory are differentially sensitive to separation timing • Some behavioral effects of maternal separation are buffered by prolonged exposure
Balakrishnan et al. (Wed,) studied this question.