The Female Rat Reproductive Cycle: A Practical Histological Guide to Staging

During preclinical investigations into the safety of drugs and chemicals, many are found to interfere with reproductive function in the female rat. This interference is commonly expressed as a change in normal morphology of the reproductive tract or a disturbance in the duration of particular phases of the estrous cycle. Such alterations can be recognized only if the pathologist has knowledge of the continuously changing histological appearance of the various components of the reproductive tract during the cycle and can accurately and consistently ascribe an individual tract to a particular phase of the cycle. Unfortunately, although comprehensive reports illustrating the normal appearance of the tract during the rat estrous cycle have been available over many years, they are generally somewhat ambiguous about distinct criteria for defining the end of one stage and the beginning of another. This detail is absolutely essential to achieve a consistent approach to staging the cycle. For the toxicologic pathologist, this report illustrates a pragmatic and practical approach to staging the estrous cycle in the rat based on personal experience and a review of the literature from the last century.