Abstract: Objective: The negative bioeffects caused by improper dietary intake of some phytoestrogens like quercetin have aroused increasing concerns. The present research used peripubertal female mice as an in vivo model to observe the effect of juvenile exposure to quercetin on breast development as indicated by the expression levels of reproductive endocrine hormone receptors and the proliferative capacity of mammary gland epithelium in adult mice. Methods: The distribution profiles of quercetin metabolites in plasma and partial breast tissue were determined by high performance liquid chromatography-quadrupole-time of flight/mass spectrometry (HPLC-Q-TOF/MS). The expression levels of estrogen (ER) and progesterone (PR) receptors and the proliferation marker proliferating cell nuclear antigen (PCNA) were detected by immunohistochemistry (IHC). Results: The contents of quercetin metabolites in breast tissue were much higher than in plasma, suggesting local accumulation of quercetin metabolites. At a dosage of 5 mg/(kg·d), quercetin dramatically increased estrogen receptor (ER)-α expression and suppressed ERβ and PR expression, thereby increasing ERα/β expression ratio in mammary gland epithelium. Conclusion: Given local accumulation of quercetin metabolites, breast tissue is very sensitive to quercetin exposure. It seems likely that peripubertal exposure to quercetin obviously alters the profile of reproductive hormone receptor expression in breast tissue during adulthood, thereby rendering the breast more sensitive to carcinogens.

Key words: quercetin, phytoestrogens, breast development, estrogen receptor α/β expression ratio