Cadmium causes delayed effects on renal function in the offspring of cadmium-contaminated pregnant female rats.
In the adult rat, chronic cadmium intoxication induces nephropathy with Fanconi-like features. This result raises the question of whether intoxication of pregnant rats has any deleterious effects on renal function in their offspring. To test this hypothesis, we measured the renal function of 2- to 60-day-old postnatal offspring from female rats administered cadmium chloride by the oral route (0.5 mg.kg(-1).day(-1)) throughout their entire gestation. Investigations of rat offspring from contaminated pregnant rats showed the presence of cadmium in the kidney at gestational day 20. After birth, the cadmium kidney concentration increased from postnatal day 2 to day 60 (PND2 to PND60), presumably because of 1) milk contamination and 2) neonatal liver cadmium content release. Although the renal parameters (glomerular filtration, U/P inulin, and urinary excretion rate) were not significantly affected until PND45, renal failure appeared at PND60, as demonstrated by a dramatic decrease of the glomerular filtration rate associated with increased excretion of the main ions. In parallel, an immunofluorescence study of tight-junction protein expression of PND60 offspring from contaminated rats showed a disorganization of the tight-junction proteins claudin-2 and claudin-5, specifically expressed in the proximal tubule and glomerulus, respectively. In contrast, expression of a distal claudin protein, claudin-3, was not affected. In conclusion, in utero exposure of cadmium leads to toxic renal effects in adult offspring. These results suggest that contamination of pregnant rats is a serious and critical hazard for renal function of their offspring.
Unité Mixte de Recherche-Centre National de la Recherche Scientifique 6548, Université de Nice-Sophia Antipolis, Nice, France.
G
G
Jacquillet
O
O
Barbier
I
I
Rubera
M
M
Tauc
A
A
Borderie
M C
MC
Namorado
D
D
Martin
G
G
Sierra
J L
JL
Reyes
P
P
Poujeol
M
M
Cougnon
D000375:Aging / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D019256:Cadmium Chloride / Q000032:analysis / Q000378:metabolism / Q000494:pharmacology*; D062507:Claudin-5; D057167:Claudins; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007365:Intercellular Junctions / Q000378:metabolism; D007477:Ions / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D007678:Kidney Glomerulus / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008892:Milk / Q000737:chemistry; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D017208:Rats, Wistar; D051437:Renal Insufficiency / Q000139:chemically induced / Q000503:physiopathology
D062507:Claudin-5; D057167:Claudins; C491874:Cldn2 protein, rat; C491510:Cldn5 protein, rat; D007477:Ions; D008565:Membrane Proteins; D019256:Cadmium Chloride