Regulation of HOXA10 expression by phytoestrogens.
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.
Akbas
G Eda
GE
Yale University School of Medicine, New Haven, CT 06520, USA.
Fei
Xiaolan
X
Taylor
Hugh S
HS
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects; D019833:Genistein / Q000009:adverse effects / Q000494:pharmacology; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007529:Isoflavones / Q000009:adverse effects / Q000494:pharmacology; D008431:Maternal-Fetal Exchange; D051379:Mice; D008815:Mice, Inbred Strains; D048789:Phytoestrogens / Q000009:adverse effects / Q000494:pharmacology*; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D020218:Response Elements / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000196:embryology* / Q000378:metabolism
D004268:DNA-Binding Proteins; D000080905:Homeobox A10 Proteins; D018398:Homeodomain Proteins; D007529:Isoflavones; D048789:Phytoestrogens; D011960:Receptors, Estrogen; C092119:Hoxa10 protein, mouse; C004742:daidzein; D019833:Genistein