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Am J Physiol Endocrinol Metab 292: E435-E442, 2007. First published September 19, 2006; doi:10.1152/ajpendo.00167.2006
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Regulation of HOXA10 expression by phytoestrogens

G. Eda Akbas, Xiaolan Fei, and Hugh S. Taylor

Yale University School of Medicine, New Haven, Connecticut

Submitted 6 April 2006 ; accepted in final form 16 September 2006

HOXA10 is necessary for normal development of the Müllerian duct, and continued adult expression in the uterus is necessary for female fertility. HOXA10 expression is altered by diethylstilbestrol, leading to uterine anomalies. Other endocrine disruptors may potentially lead to reproductive anomalies or dysfunction by altering HOXA10 expression. Here we investigated the effect of isoflavones on HOXA10 expression after in utero or adult exposure in the mouse. Genistein, but not diadzein, regulated HOXA10 mRNA and protein expression in the adult mouse uterus. In contrast, in utero genistein or diadzein exposure had no lasting effect on HOXA10 expression in the exposed offspring. Reporter gene expression driven by the HOXA10 estrogen response element was increased in a dose-responsive manner by genistein, but not daidzein. Neither estrogen receptor-{alpha} nor estrogen receptor-beta binding to the HOXA10 estrogen response element was affected by genistein or daidzein. In utero exposure to isoflavones is unlikely to result in HOXA10-mediated developmental anomalies. Adult genistein exposure alters uterine HOXA10 expression, a potential mechanism by which this agent affects fertility.

phytoestrogen; endocrine disruption; development


Address for reprint requests and other correspondence: H. S. Taylor, Division of Reproductive Endocrinology and Infertility, Dept. of Obstetrics, Gynecology, and Reproductive Sciences and Dept. of Molecular, Cellular, and Developmental Biology, Yale University School of Medicine, 333 Cedar St., P.O. Box 208063, New Haven, CT 06520 (e-mail: hugh.taylor{at}yale.edu)






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