Attenuation of cadmium-induced testicular injury in metallothionein-III null mice.
OBJECTIVE
In order to evaluate the role of metallothionein (MT)-III in cadmium (Cd)-induced testicular toxicity, we examined the sensitivity of MT-III null mice to severe testicular injury caused by Cd.


METHODS
Male MT-III null mice, MT-I/II null mice and wild-type mice were given a subcutaneous injection of CdCl(2) (15μmol/kg). The testis was collected from each mouse at 6, 12 and 24h after Cd administration.


RESULTS
Testicular hemorrhages by evaluating morphology, hemoglobin content and histological parameters in the 3 types of mice were elevated by Cd injection in a time-dependent manner. The degree of hemorrhage in Cd-injected MT-I/II null mice was similar to that in the wild-type mice. In contrast, hemorrhage in the MT-III null mice was attenuated compared with that in wild-type mice and MT-I/II null mice. Cd levels, MT-I and MT-II mRNA levels and Cd-binding molecules in the testis were similar between MT-III null mice and wild-type mice. In microarray analysis, high expression of purine-nucleoside phosphorylase 2 (Pnp2), retinal degeneration 3 (Rd3), and cadherin-like 24 (Cdh24) was revealed in the testis of MT-III null mice under normal or Cd-treated conditions.


CONCLUSIONS
MT-III null mice were found to show attenuation of Cd-induced severe testicular toxicity. These results suggest the lack of MT-III contributes to protection of testis from Cd. In addition, regulation of Pnp2, Rd3, and Cdh24 mRNA levels may involve the sensitivity of MT-III null mice to Cd.
Honda
Akiko
A
Laboratory of Pharmaceutical Health Sciences, School of Pharmacy, Aichi Gakuin University, Chikusaku, Nagoya, Japan.
Komuro
Hiroaki
H
Shimada
Akinori
A
Hasegawa
Tatsuya
T
Seko
Yoshiyuki
Y
Nagase
Hisamitsu
H
Hozumi
Isao
I
Inuzuka
Takashi
T
Hara
Hideaki
H
Fujiwara
Yasuyuki
Y
Satoh
Masahiko
M
D000818:Animals; D019256:Cadmium Chloride / Q000008:administration & dosage*; D002105:Cadmium Poisoning / Q000235:genetics / Q000378:metabolism* / Q000517:prevention & control*; D008297:Male; D000090023:Metallothionein 3; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D013733:Testicular Diseases / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D013737:Testis / Q000187:drug effects / Q000293:injuries
D000090023:Metallothionein 3; D009419:Nerve Tissue Proteins; D019256:Cadmium Chloride