title: Segregated responses of mammary gland development and vaginal opening to prepubertal genistein exposure in Bscl2(-/-) female mice with lipodystrophy.
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.
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA. Electronic address: lirong9@uga.edu.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA. Electronic address: ahmdezat@uga.edu.
authors.forename: Ahmed E
authors.initials: AE
authors.lastname: El Zowalaty
authors.affiliation: Department of Physiology, Georgia Regents University, Augusta, GA 30912, USA. Electronic address: wechen@gru.edu.
authors.forename: Weiqin
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA. Electronic address: ldudley9@uga.edu.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Dudley
authors.affiliation: Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA; Interdisciplinary Toxicology Program, University of Georgia, Athens, GA 30602, USA. Electronic address: ye@uga.edu.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Ye
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D005260:Female; D044388:GTP-Binding Protein gamma Subunits; D019833:Genistein / Q000633:toxicity*; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D052497:Lipodystrophy, Congenital Generalized / Q000150:complications* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010766:Phosphorylation; D011980:Receptors, Progesterone / Q000378:metabolism; D046468:Sexual Development; D014621:Vagina / Q000187:drug effects* / Q000254:growth & development; D015430:Weight Gain
chemical_list: C115783:Bscl2 protein, mouse; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D044388:GTP-Binding Protein gamma Subunits; D011980:Receptors, Progesterone; D019833:Genistein; D020962:Heterotrimeric GTP-Binding Proteins
keywords: Bscl2/Seipin; Genistein; Lipodystrophy; Mammary gland; Puberty; Vaginal opening