Growing up in comfort: Environmental enrichment shapes maternal approach and sex differences in offspring neuroendocrine profiles in laboratory mice.
📄 Abstract
The physical environment modulates the maternal brain and affects maternal-offspring dynamics, with downstream effects on neonatal development. In this study, we examined whether environmental enrichment (EE) influences maternal approach, neonatal ultrasonic vocalizations (USVs), and early neuroendocrine development in mice, focusing on hormonal pathways associated with maternity, stress responsivity, and gonadal hormones. Nulliparous female C57BL/6 mice were housed in EE or standard (ST) conditions prior to mating. EE cages were larger and contained extra bedding and enrichment items. Litters were culled to four pups (2/sex), and maternal approach and pup USVs were recorded on postnatal days (PND) 6 and 8 using a modified three-chamber protocol. EE dams made fewer entries into female interaction zones than ST counterparts. EE also increased USV call numbers and decreased call frequencies among pups. These effects were not sex-dependent, and despite higher emission rates, USV parameters did not correlate with maternal response in the EE group. Gene expression analyses revealed that EE altered stress- and care-related genes in the maternal brain, downregulating Prlr (prolactin receptor) and Nr3c2 (mineralocorticoid receptor) in the cortex and upregulating Prlr while downregulating Nr3c2 and Oxtr (oxytocin receptor) in the diencephalon. Further, EE housing changed neuroendocrine profiles in male pups, but not females, suggesting benefits to neurodevelopment (increased brain-derived neurotrophic factor) and alterations to sexual differentiation (Ar [androgen receptor] and Esr1 [estrogen receptor alpha]) and stress reactivity (Nr3c1 [glucocorticoid receptor] and Nr3c2). These findings highlight how environmental context can shape maternal brain and behaviour and imprint on offspring neuroendocrine development in a sex-dependent manner.