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

Abstract

Recently, we have shown thatexposure to the ultraviolet filter benzophenone-3 (BP3) during secretorydifferentiation disrupts prolactin signaling pathway and milk proteinexpression in murine mammary organoids. The present study aimed to evaluatewhether intrauterine exposure to BP3 modifies the functional differentiation ofthe 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 to 18.5. After delivery, F0 dams nursedtheir 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 littersand lactating mammary glands of F1 females were examined on LD10. BP3 exposure did not affect the body weight of theF1 females or that of their F2 litters. Intrauterine exposure to BP3significantly altered alveolar size and myoepithelial cell density atmid-lactation. However, the expression of milk proteins and the mRNA levels of Stat5aand Elf5 were similar to those of control animals. These findings reveala subclinical mammary phenotype in which intrauterine BP3 exposure altersalveolar organization and the myoepithelial compartment while preservinglactational output, consistent with a reduction in mammary functional reservewithout overt impairment of milk production or offspring growth.