Evidence of maternal resilience in two mouse strains in the context of permanent mouse breeding strategies

Abstract

Breeding female mice represent an essential but often overlooked workforce sustaining biomedical research. Despite their central role, the physiological and behavioral consequences of repeated reproductive cycles have been poorly characterized, in part because breeding animals fall outside the primary focus of laboratory animal welfare efforts, and in part because meaningful welfare readouts for laboratory rodents remain an active area of research. Here we report findings from an exploratory phenotypic study designed to capture a composite picture of maternal health in female mice of two commonly used inbred strains, BALB/cByJ and C57BL/6J, exposed to one, two, or four consecutive cycles of pregnancy and lactation, with age-matched virgin females as controls. Assessments were conducted during the final lactation period and in the five weeks following weaning, spanning behavioral, metabolic, and physiological readouts selected for their known sensitivity to reproductive or environmental challenge. Repeated reproduction altered maternal physiology, most clearly in bone microstructure, which showed progressive and dose-dependent changes across parity levels, and more subtly in body mass, energy balance, and glucose homeostasis. Behavioral readouts of maternal motivation, by contrast, remained largely stable across reproductive load. Strain differences were pervasive, underscoring that reproductive adaptation is not uniform across standard laboratory models and cautioning against generalizing from a single strain. Together, the data suggest that mouse dams demonstrate considerable resilience under intensive breeding conditions, while also highlighting that breeding shapes the maternal body in ways that accumulate across reproductive cycles and deserve greater scientific attention.