Sexual Maturation Data for CRL Sprague-Dawley Rats: Criteria and Confounding Factors

Abstract

Standardized procedures and criteria are required to provide consistent intra-laboratory values and reduce inter-laboratory differences in sexual maturation observations. When such criteria are used, these endpoints provide sensitive measures for detecting alterations in sexual maturation. However, our analyses demonstrate that the ability to detect statistically significant and biologically important differences in these endpoints is sometimes impaired by the currently common practice of evaluating only one randomly selected rat/sex/litter. Evaluation of three rats/sex/litter improved the sensitivity of the statistical analysis in detection of treatment-related effects and reduced the probability of identifying a false negative result.

Poor pubertal protein nutrition disturbs glucose-induced insulin secretion process in pancreatic islets and programs rats in adulthood to increase fat accumulation

“…In addition to the observation that the brain development of rodents reaches its peak during lactation (Morgane et al 2002), the neuronal connections do not finish at the end of the suckling phase (Sisk & Zehr 2005), which indicate that a nutritional injury, such as protein restriction during the first third of lactation, might change the brain structure and function . It is also possible that after the burst of sexual hormone release at 45-48 days of age (Lewis et al 2002), the brain is still developing neuronal connections, which allows for a nutritional maneuver to interfere with the metabolic programming when the youngest reaches adulthood. It has been shown that a stressful stimulation around the rats' pubertal period permanently changes the brain function (Tsoory et al 2010).…”

Behavioral Perturbations After Prenatal Neurogenesis Disturbance in Female Rat

“…Although a standard protocol has not yet been firmly validated to establish puberty in female rats, we have decided to choose the vaginal opening, as a visible indicator of pubertal onset in female rats (Ojeda and Urbanski 1994). Control values for vaginal opening ages ranged from post-natal day (PD) 32 to 34 with individual values for this sexual maturation parameter varying to a remarkable extent, ranging from PD 28 to 41 (Lewis et al 2002). Then, at 60 days of age, female rats are considered to have reached sexual maturity and to be adult (Spear 2000).…”

Juvenile animal toxicity study designs to support pediatric drug development

“…The selection of evaluations that make up the behavioral testing battery is flexible, but is most often similar to that used in a pre-and postnatal development study (Bailey et al, 2009). Evaluation of reproductive development is accomplished by monitoring for the age at attainment of balanopreputial separation and vaginal opening (Lewis et al, 2002). Reproductive capability of adult animals is determined by monitoring estrous cyclicity, mating animals from the same exposure groups, and performing a uterine examination during mid-gestation; this evaluation is similar to that used in adult fertility studies (Lerman et al, this issue, pages 429-436).…”