Milking it for all it’s worth: The effects of environmental enrichment on maternal nurturance, lactation quality, and offspring social behavior

Abstract

Breastfeeding confers robust benefits to offspring development in terms of growth, immunity, and neurophysiology. Similarly, improving environmental complexity (i.e., environmental enrichment; EE) contributes developmental advantages to both humans and laboratory animal models. However, the impact of environmental context on maternal care and milk quality has not been thoroughly evaluated, nor are the biological underpinnings of EE on offspring development understood. Here, Sprague-Dawley rats were housed and bred in either EE or standard-housed (SD) conditions. EE dams gave birth to a larger number of pups, and litters were standardized and cross-fostered across groups on postnatal day (P)1. Maternal milk samples were then collected on P1 (transitional milk phase) and P10 (mature milk phase) for analysis. While EE dams spent less time nursing, postnatal enrichment exposure was associated with heavier offspring bodyweights. Milk from EE mothers had increased triglyceride levels, a greater microbiome diversity, and a significantly higher abundance of bacterial families related to bodyweight and energy metabolism. These differences reflected comparable transcriptomic changes at the genome-wide level. In addition to changes in lactational quality, we observed elevated levels of cannabinoid receptor 1 in the hypothalamus of EE dams, and sex- and time-dependent effects of EE on offspring social behavior. Together, these results underscore the multidimensional impact of the combined neonatal and maternal environments on offspring development and maternal health. Moreover, they highlight potential deficiencies in the use of “gold standard” laboratory housing in the attempt to design translationally relevant animal models in biomedical research.

Significance Statement

Maternal care quality is different between environmentally enriched (EE) and standard laboratory housed (SD) dams. SD rat dams spend more time nursing their young. This may result in metabolic differences in milk quality and affect the neurodevelopmental outcomes of offspring, which are different between EE and SD animals. To test this, we evaluated milk and offspring behavior. Milk from EE dams had elevated triglyceride levels and microbiome diversity. EE offspring had heavier body weights and increased social behavior which was lost with cross-fostering into SD housing. These data identify potential deficiencies in the quality of “gold standard” laboratory housing and its impact on the welfare and design of translationally relevant animal models in biomedical research.