Whelton B D, Bhattacharyya M H, Carnes B A, Moretti E S, Peterson D P
Department of Chemistry, Eastern Washington University, Cheney.
J Toxicol Environ Health. 1988;24(3):321-43. doi: 10.1080/15287398809531165.
Female CF1 mice were bred for 6 consecutive, 42-d rounds of gestation-lactation. Their purified diets contained cadmium added at either 0.25, 5.0, or 50.0 ppm Cd; at each cadmium level, the diets were either sufficient or deficient in certain vitamins, minerals, and fat. The deficient diet at 5 ppm cadmium was designed to simulate conditions implicated in the etiology of itai-itai disease among multiparous women in Japan. Fertility, litter size, pup survival, and pup growth (weaning weight) are reported for mice on the six diets during each of the six rounds of gestation/lactation. Except for fertility, decreases in reproductive measures that occurred in response to dietary deficiencies or cadmium during round 1 of reproduction were repeated, unchanged in magnitude, in each successive round. For sufficient diet groups, 50 ppm cadmium had no effect on fertility or pup survival during lactation, but caused a 15% decrease in litter size at birth and a 25% decrease in pup growth. Dietary deficiencies alone decreased all four measures of reproductive performance: fertility by 12%, litter size by 30%, pup survival by 18%, and pup growth by 42%. In addition, dietary deficiencies strikingly decreased the incidence of consecutive pregnancies. Combined effects of 50 ppm cadmium and dietary deficiencies were additive for all reproductive measures except fertility; for fertility, cadmium caused no decrease in the fertility of sufficient-diet animals, but caused a striking 45% decrease in deficient-diet animals. Relating our results to humans, women who contracted itai-itai disease (analogous to mice on the deficient, 5 ppm cadmium diet), in addition to their characteristic bone disease, could have experienced decreases in fertility and in growth of their offspring related to their dietary deficiencies. In addition, their diet-related decreases in fertility could have been enhanced by their combined exposure to cadmium.
雌性CF1小鼠连续繁殖6轮，每轮妊娠期和哺乳期为42天。它们的纯化日粮添加了镉，添加量分别为0.25、5.0或50.0 ppm Cd；在每个镉水平下，日粮在某些维生素、矿物质和脂肪方面要么充足要么缺乏。5 ppm镉的缺乏日粮旨在模拟日本多产妇女中与痛痛病病因相关的情况。报告了六轮妊娠/哺乳期内六组日粮喂养小鼠的生育力、窝仔数、幼崽存活率和幼崽生长情况（断奶体重）。除生育力外，在第一轮繁殖中因日粮缺乏或镉暴露而出现的生殖指标下降在随后的每一轮中都重复出现，且幅度不变。对于日粮充足的组，50 ppm镉对哺乳期的生育力或幼崽存活率没有影响，但导致出生时窝仔数减少15%，幼崽生长减少25%。仅日粮缺乏就降低了所有四项生殖性能指标：生育力降低12%，窝仔数降低30%，幼崽存活率降低18%，幼崽生长降低42%。此外，日粮缺乏显著降低了连续妊娠的发生率。50 ppm镉和日粮缺乏对所有生殖指标（除生育力外）的联合作用是相加的；对于生育力，镉没有降低日粮充足动物的生育力，但使日粮缺乏动物的生育力显著降低了45%。将我们的结果与人类联系起来，患痛痛病的女性（类似于食用缺乏、含5 ppm镉日粮的小鼠），除了患有特征性的骨病外，可能还因日粮缺乏而生育力下降，后代生长受限。此外，她们因饮食导致的生育力下降可能因镉的联合暴露而加剧。
