Maternal age, fertility and failure of teratogenicity by trypan blue in Jcl:SD rats

The study compared the fertility of nulliparous Jcl:SD rats, young mature (12-week-old) versus middle aged (47-week-old) or old animals (64-week-old), both groups near the termination of their reproductive capability. Trypan blue (TB) was given subcutaneously at 0 (control), 10 or 50 mg/kg on days 7 through 9 of gestation to increase the malformation rate. However, no clear teratogenic action of TB was observed. The dose of 10 mg/kg TB was well tolerated, while 50 mg/kg was of severe maternal toxicity and 14 of 53 females died. In comparison with the young control group, the average per litter from middle aged or old dams was significantly decreased for implantation sites, live fetuses and fetal weight, while the percentages of pre-implantation loss and dead implants were extremely high. No increase of the malformation rate occurred with maternal aging. Histologically, middle aged and old rats exhibited age-related lesions of the pituitary, adrenals and reproductive organs with pituitary adenomas, cystic endometrium and sclerotic atrophy of uterine glands being significantly increased in non-pregnant, old rats.