Pre-but not post-natal nutritional restriction promotes mammary development

Abstract

The mammary gland undergoes continuous growth, differentiation, and cyclical remodeling throughout the whole life, with morphogenesis from the embryonic stage to adulthood being crucial and highly sensitive to nutritional supply. While moderate nutritional restriction in early life and subsequent restore can promote the tissues development such as muscle, its effects on the mammary remain largely unexplored and appear to depend critically on the development stage. Thus, the effects of moderated nutritional restriction in early life including embryonic (ER), suckling (SR), or pubertal (PR) periods on mammary development and subsequent lactation performance in mice were investigated in the present study. In this study, we imposed nutritional restriction on mice during either a single period or two periods. Mammary gland and serum samples were collected at maturity (56 d) and on lactation day 15 for hormonal, histological, and transcriptomic analyses. Our results demonstrate that ER enhances mammary development and adult lactation capacity by boosting proliferative activity and increasing the mammary stem cell content. In contrast, postnatal nutritional restrictions (SR and PR) disrupt normal gland morphogenesis by attenuating hormonal signaling responses and reducing stromal tissue remodeling. Notably, the adverse effects of SR on mammary morphology are reversible upon nutritional repletion, with no subsequent impact on milk production, whereas PR leads to a significant impairment in adult lactation. These findings reveal distinct regulatory mechanisms of nutritional intervention at various development stages and provide a foundational basis for optimizing lactational outcomes through targeted nutritional strategies.