Segregated responses of mammary gland development and vaginal opening to prepubertal genistein exposure in Bscl2−/− female mice with lipodystrophy

摘要

Berardinelli-Seip congenital lipodystrophy 2-deficient (Bscl2^−/−) mice recapitulate human BSCL2 disease with lipodystrophy. Bscl2-encoded seipin is detected in adipocytes and epithelium of mammary gland. Postnatal mammary gland growth spurt and vaginal opening signify pubertal onset in female mice. Bscl2^−/− females have longer and dilated mammary gland ducts at 5-week old and delayed vaginal opening. Prepubertal exposure to 500 ppm genistein diet increases mammary gland area and accelerates vaginal opening in both control and Bscl2^−/− females. However, genistein treatment increases ductal length in control but not Bscl2^−/− females. Neither prepubertal genistein treatment nor Bscl2-deficiency affects phospho-estrogen receptor α or progesterone receptor expression patterns in 5-week old mammary gland. Interestingly, Bscl2-deficiency specifically reduces estrogen receptor β expression in mammary gland ductal epithelium. In summary, Bscl2^−/− females have accelerated postnatal mammary ductal development but delayed vaginal opening; they display segregated responses in mammary gland development and vaginal opening to prepubertal genistein treatment.