Sex-specific effects of neonatal exposures to low levels of cadmium through maternal milk on development and immune functions of juvenile and adult rats.
Cadmium (Cd) is a major environmental contaminant. Although immunotoxic effects have been associated with Cd exposure, the inconsistency of experimental results underlines the need of an experimental approach more closely related to environmental conditions. We investigated the effects of exposing neonatal Sprague-Dawley rats to environmentally relevant doses of Cd through maternal milk. Dams received 10 parts per billion (ppb) or 5 parts per million (ppm) Cd chloride (CdCl2) in drinking water from parturition until the weaning of the pups. Half of the offspring was sampled at weaning time. The remaining juvenile rats received water without addition of Cd until adulthood. Cd accumulation in kidneys of juvenile rats fed from dams exposed to Cd indicated the transfer of the metal from mother to pups through maternal milk. This neonatal exposure resulted in decreased body, kidney and spleen weights of just weaned females but not of males. This effect was more pronounced in the less exposed females fed from dams exposed to 10 ppb Cd, which also displayed lower hepatic metallothionein-1 (MT-1) mRNA levels. The effect of Cd exposure on body and organ weights did not persist to adulthood. In contrast, we observed gender-specific effects of neonatal Cd exposure on the cytotoxic activity of splenic NK-cells of both juvenile and adult rats. Cd also strongly inhibited the proliferative response of Con A-stimulated thymocytes in both male and female adult rats 5 weeks after the cessation of Cd exposure. These immunotoxic effects were observed at doses much lower than those reported to produce similar effects when exposure occurred during adulthood. In conclusion, neonatal exposures to environmentally relevant levels of Cd through maternal milk represent a critical hazard liable to lead to both transitory and persistent immunotoxic effects.
Pillet
Stéphane
S
INRS-Institut Armand-Frappier, Université du Québec, 245 Hymus Boulevard, Pointe-Claire, Que., Canada H9R 1G6.
Rooney
Andrew A
AA
Bouquegneau
Jean-Marie
JM
Cyr
Daniel G
DG
Fournier
Michel
M
D000818:Animals; D000831:Animals, Newborn; D001402:B-Lymphocytes / Q000187:drug effects; D002104:Cadmium / Q000032:analysis / Q000633:toxicity*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004785:Environmental Pollutants / Q000032:analysis / Q000633:toxicity*; D005260:Female; D007668:Kidney / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D007774:Lactation; D008099:Liver / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors; D013154:Spleen / Q000187:drug effects / Q000254:growth & development / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
D004785:Environmental Pollutants; D012333:RNA, Messenger; D002104:Cadmium; D008668:Metallothionein