Developmental exposure of rats to a reconstituted PCB mixture or aroclor 1254: effects on organ weights, aromatase activity, sex hormone levels, and sweet preference behavior.
Polychlorinated biphenyls (PCBs) are lipophilic industrial chemicals which are regularly detected in human breast milk, serum, and tissues. They possess hormone-modulating properties, and, when transferred transplacentally to the developing fetus, PCBs have been shown to induce persistent sex-specific neurobehavioral deficits. Interactions of PCBs with sex steroid-modulated neural differentiation could in part account for such effects. To test this hypothesis, female Long-Evans rats were exposed via food containing 40 mg/kg of either a reconstituted PCB mixture (RM), composed according to the congener-pattern in human breast milk, or the technical PCB mixture Aroclor 1254 (A1254). The exposure period started 50 days prior to mating and was terminated at birth (postnatal day 0: PND 0). Aromatase (CYP 19) activity was determined in hypothalamus/preoptic area (HPOA) brain-sections from newborn male pups. This enzyme converts testosterone (T) to 17beta-estradiol (E(2)) and plays a key role in sexual brain differentiation. Moreover, serum concentrations of T and E(2), physical development, organ weights, exposure levels, and sex-specific behavior were evaluated at different life stages. On PND 0, a reduced aromatase activity was detected in the HPOA of male RM-pups compared to controls. Female RM-weanlings exhibited significantly elevated uterine wet weights on PND 21, which is a marker for estrogenic activity. In the adult stage (PND 170), male offspring with maternal exposure to either PCB mixture showed markedly reduced testes weights and serum testosterone levels, thus demonstrating persistent antiandrogenic effects. On PND 180, male RM-rats exhibited a behavioral feminization in a sweet preference test, suggesting long-lasting changes in neuronal brain organization caused by the perinatally suppressed aromatase activity. The results suggest that maternal exposure to the RM, the pattern of which is similar to the PCB spectrum in human milk, results in more distinct effects on sex steroid-dependent processes and behavior than the technical PCB mixture A1254. PCB levels in brain and adipose tissue of the exposed offspring lay within 1-2 orders of magnitude above background concentrations in humans.
Hany
J
J
Medical Institute of Environmental Hygiene, Düsseldorf, D-40225, Germany. hany@rz.uni-duesseldorf.de
Lilienthal
H
H
Sarasin
A
A
Roth-Härer
A
A
Fastabend
A
A
Dunemann
L
L
Lichtensteiger
W
W
Winneke
G
G
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D001141:Aromatase / Q000378:metabolism*; D001724:Birth Weight / Q000187:drug effects; D001921:Brain / Q000201:enzymology; D020111:Chlorodiphenyl (54% Chlorine) / Q000633:toxicity; D004785:Environmental Pollutants / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D004958:Estradiol / Q000097:blood; D005260:Female; D005518:Food Preferences / Q000187:drug effects*; D012739:Gonadal Steroid Hormones / Q000097:blood*; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009929:Organ Size / Q000187:drug effects; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D051381:Rats; D020318:Rats, Long-Evans; D012439:Saccharin / Q000494:pharmacology; D012737:Sex Factors; D013549:Sweetening Agents / Q000494:pharmacology; D013739:Testosterone / Q000097:blood
D004785:Environmental Pollutants; D012739:Gonadal Steroid Hormones; D013549:Sweetening Agents; D020111:Chlorodiphenyl (54% Chlorine); D013739:Testosterone; D004958:Estradiol; D011078:Polychlorinated Biphenyls; D001141:Aromatase; D012439:Saccharin