Maternal-pup directional iron transfer is mediated by changes in muscle iron exporter and receptor expression in pinnipeds

Marine mammal milk contains up to 100x more iron than that of terrestrial mammals, reflecting exceptional maternal-offspring iron transfer that supports heme-based body oxygen store development in pups. In capital breeders, this iron derives from adult females’ endogenous stores, including from muscle. High circulating iron levels during pinniped lactation are paradoxically associated with iron export, rather than uptake, in adult female seals. However, we lack an understanding of the transcriptional changes modulating iron mobilization in pinnipeds, particularly for tissues with high iron demands such as muscle. To address this gap, we quantified relative expression of iron-regulatory genes in swimming muscle (longissimus dorsi) from Weddell seal (Leptonychotes weddellii) and grey seal (Halichoerus grypus) adult females and pups throughout lactation (adult females: early, late, post-lactation; pups: late, post-lactation) using RT-qPCR with ‘late lactation pups’ as the control. Ferroportin (FPN1) expression was 3.1- to 7.9-fold higher in lactating adult females than in pups (p< 0.0001 in each species), peaking late in lactation. Transferrin receptor (TFR1) expression was downregulated in adult females compared to pups (Weddell seal: 6.7- to 12.5-fold lower in adult females vs. pups, p< 0.0001; grey seal: 11- to 33-fold lower in adult females vs. pups, p< 0.0001), indicating reduced transferrin-dependent iron uptake in adult females. Interestingly, TFR1 expression in Weddell seal adult females remained low post-lactation (6-fold lower in adult females than in pups; p< 0.0001). In contrast, divalent metal transporter (DMT1) expression was elevated 1.7- to 3.4-fold in adult females compared to pups (p< 0.0001 in each species) with the highest expression occurring in adult females late in lactation, suggesting that adult females rely on non-transferrin-mediated iron uptake to meet cellular iron demands despite high transferrin saturations during lactation. Together, these coordinated gene expression changes and the decoupling of high transferrin saturations from transferrin-mediated iron uptake in adult female seals likely facilitate directional iron transfer from female to pup during lactation. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.