Genistein Inhibits Intestinal Cell Proliferation in Piglets
AN-CHIAN CHEN, MARK A. BERHOW, KELLY A. TAPPENDEN and SHARON M. DONOVAN
Division of Nutritional Sciences [A.-C.C., K.A.T., S.M.D.], University of Illinois at Urbana-Champaign, Urbana, IL 61801; and United States Department of Agriculture [M.A.B.], Agricultural Research Service, National Center for Agricultural Utilization Research, Peoria, IL 61604
Correspondence: Sharon M. Donovan, Ph.D., R.D., 457 Bevier Hall, 905 S. Goodwin Avenue, Urbana, IL 61801; e-mail: sdonovan@uiuc.edu
Currently 15% of U.S. infants are fed soy formulas that contain up to 14 mg of genistein equivalents/L. Our goal was to investigate the impact of dietary genistein on intestinal development. Piglets (n = 8/group) were fed sow milk replacer (MR), MR + 1 mg/L of genistein (LG), or MR + 14 mg/L of genistein (HG) for 10 d. Formula intake, weight gain, and intestinal length and weight were similar in all groups. Average serum genistein concentration in the HG group was similar to that of soy formula&endash;fed infants. No significant effects of genistein on enterocyte apoptosis, lactase, and sucrase activities or electrophysiologic measures were observed in jejunum or ileum. Jejunal and ileal villus heights were not significantly different, but the percentage of proliferating cell nuclear antigen&endash;positive jejunal crypt cells in the HG was reduced 50% compared with that in MR and LG (p = 0.001), indicating decreased proliferation. Enterocyte migration distance in the HG group tended to be 20% less (p = 0.1) than LG or MR. Jejunal estrogen receptor RNA expression in HG was half of that in LG (p = 0.05), but neither was significantly different from MR. In conclusion, genistein at the level present in soy infant formula is bioactive in the small intestine and results in reduced enterocyte proliferation and migration. The lack of effect of genistein on nutrient transport and enzyme activity suggests that the impact of genistein is greater on proliferating versus differentiated intestinal cells.
Abbreviations:
BrdU, 5'-bromodeoxyuridine
ER, estrogen receptor
HG, high genistein
ITF, intestinal trefoil factor
LC-MS, liquid chromatography-mass spectrometry
LG, low genistein
LPH, lactase phlorizin hydrolase
MR, milk-replacer
PCNA, proliferating cell nuclear antigen
SP, spasmolytic polypeptide
TFF, trefoil factor