Intrauterine benzophenone-3 exposure alters mammary gland architecture without impairing lactational performance

Recently, we have shown that exposure to the ultraviolet filter benzophenone-3 (BP3) during secretory differentiation disrupts prolactin signaling pathway and milk protein expression in murine mammary organoids. The present study aimed to evaluate whether intrauterine exposure to BP3 modifies the functional differentiation of the lactating mammary gland in F1 female mice. To this end, pregnant mice (F0) were dermally exposed to BP3 (0.15 or 50 mg/kg/day) or the control vehicle (sesame oil), from gestation days 8.5-18.5. After delivery, F0 dams nursed their pups, and F1 female offspring were subsequently bred at 8 weeks of age. Lactation day (LD) 1 was defined as the day following the birth of F2 litters and lactating mammary glands of F1 females were examined on LD10. BP3 exposure did not affect the body weight of the F1 females or that of their F2 litters. Intrauterine exposure to BP3 significantly altered alveolar size and myoepithelial cell density at mid-lactation. However, the expression of milk proteins and the mRNA levels of Stat5a and Elf5 were similar to those of control animals. These findings reveal a subclinical mammary phenotype in which intrauterine BP3 exposure alters alveolar organization and the myoepithelial compartment while preserving lactational output, consistent with a reduction in mammary functional reserve without overt impairment of milk production or offspring growth.