ALTERATIONS IN THE REPRODUCTIVE PATTERNS OF FEMALE MICE EXPOSED TO XENOBIOTICS

Chemicals, by virtue of their varied interactions with biological mole cules, are expected to differ in the way they may alter female reprodu ction. Reproductive toxicity may reflect effects either on the female germ cells or on various maternal processes such as ovulation, implant ation, pregnancy, and parturition. In either case, the ultimate manife station of chemical toxicity on female reproduction is a decrease in t he number of normal young born. Very little information is available o n the effects of chemicals that are nonhormonal in nature on the long- term ability of treated females to produce offspring. This report pres ents the results of long-term female total reproductive capacity (TRC) tests on 29 chemicals, including pharmaceuticals, pesticides, and alk ylating and industrial agents. For each chemical, the minimum test inv olved an evaluation of the maximum tolerated dose administered as a si ngle intraperitoneal injection. Females were single-pair mated with an untreated male for most of the female's reproductive life span (a min imum of 347 days posttreatment) and scored for the number of live birt hs produced during this period. Confirmatory dominant lethal experimen ts or histological examinations for numbers of small follicles were ca rried out when mutagenic effects or cytotoxicity, respectively, were s uspected as the basis for reduced fertility. Of the 29 chemicals studi ed, 17 had reproductive effects which may be grouped into one of three classes: (1) those that reduced the total number of young and litters per female, (2) those that reduced the total number of young but not of litters, and (3) those that had no significant effect on the total number of young produced but reduced the size of the first and/or seco nd litters. The TRC provides a capacity for detecting a range of toxic insults upon female reproduction. Many of the chemicals were indeed s hown to affect the reproductive performance of females through mutagen ic and/or cytotoxic effects on follicles. In some cases, however, no c ausative mechanism could be identified for the observed reduction in r eproductive performance. Nevertheless, with this report the number of chemicals tested by this TRC procedure has been quadrupled and the cat egories of chemicals tested have been substantially broadened. (C) 199 7 Society of Toxicology.