Normal mammary gland morphology in pubertal female mice following in utero and lactational exposure to genistein at levels comparable to human dietary exposure.
The objective of the study was to determine the effect of in utero and lactational exposure to genistein (0, 0.1, 0.5, 2.5 and 10 mg/kg/day) on mammary gland morphology in female B6D2F1 mice at levels comparable to or greater than human exposures. The effect of diethylstilbestrol (DES; 0, 0.1, 1, 10 microg/kg/day) on the mammary gland was also examined as a positive estrogenic control. Pregnant females were treated by daily gavage from gestational day 12 to postnatal day (PND) 20. Female offspring were weaned on PND21 and mammary gland whole mounts were examined for growth (length and area of the epithelial tree), proliferation (number of terminal end buds (TEBs)), and differentiation (density of alveolar buds (ABs)) on PND49. The highest dose of DES induced a significant increase in mammary gland growth (P<0.05) and also decreased the number of TEBs (P<0.06). The density of ABs was not significantly affected by DES. By contrast to DES, genistein had no effect on mammary gland morphology at any dose. These results suggest that in utero and lactational exposure to genistein at levels comparable to or greater than human exposures do not adversely affect mammary gland development in pubertal female B6D2F1 mice.
Department of Biochemistry and Molecular Biology, National Food Safety and Toxicology Center, Institute for Environmental Toxicology, Michigan State University, East Lansing, USA.
Mark R
MR
Fielden
Cora J
CJ
Fong
Sandra Z
SZ
Haslam
Tim R
TR
Zacharewski
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D004032:Diet; D005260:Female; D019833:Genistein / Q000494:pharmacology*; D006128:Growth / Q000187:drug effects; D007774:Lactation / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000254:growth & development*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012741:Sexual Maturation / Q000502:physiology*
D016588:Anticarcinogenic Agents; D019833:Genistein