Prenatal Edible Bird’s Nest Supplementation Attenuates Offspring Skin Pigmentation via Dual Inhibition of CREB and ERK Signaling to Downregulate MITF-TYR Axis

Background/Objectives: Edible bird’s nest (EBN) benefits skin, but its transgenerational effects are unknown. This study investigated whether maternal EBN or its key component, sialic acid (SA), could program offspring skin pigmentation and antioxidant capacity. Methods: Pregnant Sprague-Dawley rats were supplemented with EBN or equi-sialic acid SA. Offspring skin brightness (L*, ITA°), melanin content, and key molecular targets (e.g., MITF, TYR, TRP1/2, PMEL, RAB27A, p-CREB, p-ERK, CAT, GCS, MDA) were assessed at postnatal days 0–21. Results: Maternal EBN induced a dose-dependent skin-brightening effect in offspring. High-dose EBN increased skin L* by 10.46% and ITA° by 14.28%, while reducing total melanin by 26.77%. This was mediated by downregulation of the MITF-TYR/TRP axis and its upstream CREB/ERK signaling, suppression of melanosome transport proteins (PMEL, RAB27A), and enhancement of antioxidant defenses (increased CAT/GCS, decreased MDA). SA alone showed similar but weaker effects. Conclusions: This study demonstrates that maternal EBN intake programs offspring skin towards a lighter phenotype and enhanced antioxidant status through multi-faceted regulation of melanogenesis. The superior efficacy of whole EBN over pure SA highlights the value of the intact food matrix, suggesting EBN as a promising functional food for maternal nutrition.