Neonatal exposure to the phytoestrogen genistein alters mammary gland growth and developmental programming of hormone receptor levels.

Abstract:

:Developmental effects of genistein (Gen) on the mammary gland were investigated using outbred female CD-1 mice treated neonatally on d 1-5 by sc injections at doses of 0.5, 5, or 50 mg/kg.d. Examination of mammary gland whole mounts (no. 4) before puberty (4 wk) revealed no morphological differences in development after Gen treatment. However, mice treated with Gen-50 had stunted development characterized by less branching at 5 wk and decreased numbers of terminal end buds at 5 and 6 wk. Conversely, at 6 wk, Gen-0.5-treated mice exhibited advanced development with increased ductal elongation compared with controls. Measurements of hormone receptor levels showed increased levels of progesterone receptor protein and estrogen receptor-beta mRNA in Gen-0.5-treated mice compared with controls; ERalpha expression was decreased after all doses of Gen treatment. Lactation ability, measured by pup weight gain and survival, was not affected after neonatal Gen-0.5 and Gen-5. Mice treated with Gen-50 did not deliver live pups; therefore, lactation ability could not be determined. Evaluation of mammary glands in aged mice (9 months) showed no differences between Gen-0.5-treated mice and controls but mice treated with Gen-5 and Gen-50 exhibited altered morphology including reduced lobular alveolar development, dilated ducts, and focal areas of "beaded" ducts lined with hyperplastic ductal epithelium. In summary, neonatal Gen exposure altered mammary gland growth and development as well as hormone receptor levels at all doses examined; higher doses of Gen led to permanent long-lasting morphological changes.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Padilla-Banks E,Jefferson WN,Newbold RR

doi

10.1210/en.2006-0389

subject

Has Abstract

pub_date

2006-10-01 00:00:00

pages

4871-82

issue

10

eissn

0013-7227

issn

1945-7170

pii

en.2006-0389

journal_volume

147

pub_type

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