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

Reprod Toxicol. 2015 Jul:54:76-83. doi: 10.1016/j.reprotox.2014.10.023. Epub 2014 Nov 5.

Abstract

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 500ppm 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.

Keywords: Bscl2/Seipin; Genistein; Lipodystrophy; Mammary gland; Puberty; Vaginal opening.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Animals
  • Disease Models, Animal
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Female
  • GTP-Binding Protein gamma Subunits
  • Genistein / toxicity*
  • Heterotrimeric GTP-Binding Proteins / deficiency*
  • Heterotrimeric GTP-Binding Proteins / genetics
  • Lipodystrophy, Congenital Generalized / complications*
  • Lipodystrophy, Congenital Generalized / genetics
  • Lipodystrophy, Congenital Generalized / metabolism
  • Lipodystrophy, Congenital Generalized / pathology
  • Mammary Glands, Animal / drug effects*
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / metabolism
  • Mammary Glands, Animal / pathology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Phosphorylation
  • Receptors, Progesterone / metabolism
  • Sexual Development
  • Vagina / drug effects*
  • Vagina / growth & development
  • Weight Gain

Substances

  • Bscl2 protein, mouse
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • GTP-Binding Protein gamma Subunits
  • Receptors, Progesterone
  • Genistein
  • Heterotrimeric GTP-Binding Proteins