Early postpartum development of pup urine preference in mothers

The transition to motherhood involves profound physiological and neural changes, including adaptations in the sensory systems that support infant care. ^1,2 While the olfactory system plays a critical role in guiding maternal behaviors such as pup retrieval and nesting, ^3,4 how olfactory processing itself is reshaped during motherhood remains poorly understood. Here, we show that first-time mothers develop a selective preference for pup urine following parturition and early postpartum care, a preference not observed for other social or neutral odors. Using odor preference assays combined with liquid and gas chromatography–mass spectrometry, we identify specific volatile compounds in pup urine that may contribute to this maternal attraction. Disruption of olfactory input or restriction of contact chemosensation abolished the preference, indicating that both volatile and non-volatile sensory modalities contribute, likely through combined input from the main olfactory epithelium (MOE) and vomeronasal organ (VNO). ^5,6 Notably, this preference is absent in late-pregnant females, in mothers separated from pups at birth, and in virgins cohoused with pups or exposed to pup urine-highlighting that pup urine preference depends on the convergence of internal hormonal signals and external chemosensory cues. ^7,8 These findings reveal a previously unrecognized specificity in maternal olfactory behavior and provide insight into how motherhood modulates the sense of smell to support offspring recognition and care.