Transplacental exposure to indole-3-carbinol induces sex-specific expression of CYP1A1 and CYP1B1 in the liver of Fischer 344 neonatal rats.
Indole-3-carbinol (I3C), a naturally occurring component of broccoli, cabbage, and other members of the family Cruciferae, is a tumor modulator in several animal models that demonstrates significant chemoprevention against development of both spontaneous and chemically induced cancers while conversely eliciting tumor promoter effects in others. This study examines the disposition of I3C in the pregnant rat model, specifically to determine whether I3C can traverse the maternal placenta, and what effects, if any, are elicited in the neonate. We now report that dietary I3C treatment of pregnant female rats results in appearance of I3C acid condensation products in both maternal and neonatal livers. Livers from I3C-fed maternal rats showed CYP1A1 protein induction; however, no CYP1B1 protein was detected. No CYP1A1 or CYP1B1 protein was detected in the livers of pregnant controls or their offspring. We also report a sex-specific induction of CYP1A1 and CYP1B1 protein in livers from newborns born to I3C-fed dams. CYP1A1 protein was significantly induced in male neonatal liver, but not in females. Conversely, hepatic CYP1B1 protein was induced to high levels in female neonates, with no CYP1B1 protein detected in male littermates. Our results demonstrate that dietary I3C acid condensation products can cross the maternal placenta and differentially induce neonatal hepatic CYP1A1 and CYP1B1 in a sex-specific manner. The results highlight the potential of I3C to effect changes in the overall metabolic profile of xenobiotics to which the fetus is exposed transplacentally and indicate the possible involvement of sex-specific modulators in Ah receptor-mediated responses in this model.
Larsen-Su
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Department of Environmental and Molecular Toxicology, 571 Weniger Hall, Oregon State University, Corvallis, OR 97331-6512, USA.
Williams
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D000818:Animals; D000831:Animals, Newborn; D000975:Antioxidants / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D065633:Cytochrome P-450 CYP1B1; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D007211:Indoles / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008431:Maternal-Fetal Exchange / Q000502:physiology; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D051381:Rats; D011916:Rats, Inbred F344; D012737:Sex Factors
D000975:Antioxidants; D007211:Indoles; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol; D001189:Aryl Hydrocarbon Hydroxylases; C585499:Cyp1b1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1