Kidney changes in multiparous, nulliparous and ovariectomized mice fed either a nutrient-sufficient or -deficient diet containing cadmium

As a simulation of the etiological factors known for Itai-Itai disease, a syndrome characterized by renal dysfunction and osteomalacia in its Japanese victims, female mice were subjected to the individual and combined stresses of dietary Cd, nutrient-deficient diet, multiparity and ovariectomy. Renal function as affected by the etiological factors was periodically evaluated by determination of protein, amino acid, glucose and Cd concentrations in urine; periodic changes in skeletal Ca status were assessed relative to current renal function. Renal metabolism of Cd, Zn and Cu was also examined. At age 68 days, female mice were given nutrient-sufficient (+) or -deficient (−), purified diets containing either 0.25 (environmental), 5, or 50 ppm Cd as CdCl 2; the nutritional composition of (−) diet simulated that of food consumed by Japanese victims of Itai-Itai disease. At age 70 days, half of the females began a breeding regimen of six consecutive, 42-day rounds of pregnancy/lactation (PL mice); the remainder were maintained as virgin, non-pregnant controls (NP mice). Limited numbers of PL and NP mice were sacrificed at the end of each reproductive round. PL(+) mice taken in a given round had successively borne litters in that round and all preceding ones. PL(−) females taken at the end of round (R)-l, -2 and -3 had successively borne litters through those rounds; those taken at the end of R-5 or R-6 had nonsuccessively borne litters in four of five or three of six rounds, respectively. At the conclusion of the 252-day reproductive period, remaining females entered the 392-day, post-reproductive phase of the experiment. At age 546 days (mid-R-12), PL females having successfully borne at least three litters were ovariectomized (OV) to mimic human menopause; at the same time, NP females were either ovariectomized or sham-operated (SO). After surgery, all females were maintained to age 714 days (mid-R-16), then sacrificed. Spot urine samples were taken from individual mice at the end of most reproductive rounds (R-2 → 6), prior to surgery (rnid-R-10), and prior to final sacrifice (late-R-15); samples were also collected via metabolism cages at the end of R-10. Food consumption, monitored on a weekly basis over the first nine rounds, was generally not significantly affected by dietary Cd level or nutrient deficiencies in females of the same reproductive status; consumption was increased about 2.5-fold in PL versus NP groups during the reproductive period and about