[Rats' reproductive function under toxic load against the background of protein deficiency].

Abstract

Safety assessment approaches of novel food, currently adopted in the Russian Federation, imply mandatory in vivo reproductive toxicity tests with the study of reproductive function and offspring development in order to obtain comprehensive evidence of the absence of distant adverse effects that may manifest only in the next generation. Comprehensive study of reproductive function, pre- and postnatal offspring development, as a rule, includes the research of a large number of parameters, all of which has a wide range of physiological fluctuations, and the heterogeneous distribution of some parameters' values complicates the interpretation of the results. The purpose of the study was to investigate the efficiency of a reduced adaptive potential model in rats, based on decreased diet protein intake, for the use in reproductive toxicity experiments. Material and methods. The research lasting 155 days was carried out on rats of F0 (180 females and 90 males) and F1 (773 pups, 456 fetuses) generations. Animals of parental generation F0 were divided into 3 groups - control, the 1st and the 2nd test groups, 30 males and 60 females in each. The initial age of F0 rats was 28-35 days. Animals of all groups during growth and sexual maturation (25-90 days of life) received a diet with reduced protein content (9.4 g per 100 g of diet, which is 9% in calorie value). After reaching the age of physiological maturity (100 days) rats were transferred to a diet with lower protein content (6.1 g per 100 g of diet, 6% in calorie value), and received this diet during mating, pregnancy and feeding of F1 offspring. The rats of the test groups received with feed the model herbicide glyphosate (isopropylamine salt, concentration 360 g/l) at a dose of 0.3 g/kg body weight (6% of LD50): the 1st test group - from day 70 of life, the 2nd test group - from day 30 of life throughout the duration of the experiment. Reproductive function was evaluated by the fertility of F0 animals and by the character of prenatal and postnatal development of F1 offspring. Results. The toxic factor's influence on the background of reduced protein supply did not lead to complex changes in the reproductive function of rats, the test groups differed from the control group only by the post-implantation loss and the mean litter size in the postnatal period: post-implantation loss in the 1st and the 2nd test groups was higher than normal, exceeding the value of this indicator in the control group (4.7±1.6%) by 3.1 (p<0.05) и 2.2 (р>0.05) times; the mean litter size in the 1st and the 2nd test groups was by 15.8 and 21.3% (р<0.05) lower than in the control group. Survival rate of offspring during the 1st month of life in all groups was at least 72%, which corresponds to the lower limit of the norm characteristic for Wistar rats. Conclusion. The use of the alimentary model of adaptation potential reduction based on diet protein deficiency does not consider appropriate in reproductive toxicity studies, since it does not increase either the severity of the reaction to toxic effects or the reliability of the results obtained. This model can be recommended for subacute toxicological studies of low-toxicity objects, in particular, when assessing the safety of novel food.