A Practical Approach, Second Edition=Ronald D. Ho.pdf

DEVELOPMENTAL AND REPRODUCTIVE TOXICITY STUDY FINDINGS 393Table 9.36Historically observed functional reproductive indicesfor [Crl:CD ® (SD)IGS BR rats] aMean(%)25thQuartile (%)75thQuartile (%)Male Mating IndexNo. of males with evidence of matingTotal no. of males used for matingFemale Mating IndexNo. of females with evidenceof mating (or confirmed pregnancy)Total no. of females used for mating× 100 96.1 95.0 100.0× 100 97.3 95.9 100.0Male Fertility IndexNo. of males siring a litterTotal no. of males used for mating× 100 89.6 86.7 95.0Female Fertility IndexNo. of femaleswith confirmed pregnancyTotal no. of females used for mating× 100 90.9 88.0 96.0Source: Data from WIL Research Laboratories, Inc. historical control database.in the CNS or from imbalances in hormonal cascades. Indirect measures of mating performanceare obtained by observing either the presence of sperm from a vaginal lavage (microscopically) ora copulatory plug in the vagina or below the mating cage. The latter observation technique mayalso be used for the mouse. However, results are more variable, and the endpoint becomes lesssensitive because retention of the vaginal plug is longer and mistiming of pregnancy may be aconsequence. The process of confirming that coitus has occurred is confounded because, evenamong the most technically skilled, the rate of proficiency of timing the event by vaginal lavageis only 90% to 93%, in the authors’ experience. Thus, up to 10% of the data for a given breedingcycle may be unavailable for the final interpretation. For this reason, differences in the matingindex that represent one or two fewer successful matings in a group should not cause an increasedlevel of concern. However, decrements in this endpoint may also signal that abnormalities havebeen introduced. Such abnormalities may consist of changes in the duration and/or the orderlysequence of stages of the rodent estrous cycle, or they can also arise from deficits in sperm quality.These decrements may occur in the presence of disturbances in the elapsed time between the startof cohabitation and observed evidence of mating (referred to as the precoital interval). The precoitalinterval is usually reported as a fraction of the number of days required for mating. Most rodentswould be expected to show evidence of mating within the first estrous cycle (4 or 5 days). It isnoteworthy that normal precoital intervals may occur without successful impregnation if effects onintromission are observed. In addition, the females are rarely synchronized at the onset of thebreeding period in terms of stage of estrus, and statistical transformations may be necessary toaccount for these variations. In essence, to determine biological significance of differences in groupmean data of less than two days between treated groups and the control group, one must includea detailed assessment of the individual data.On rare occasions, an unexpectedly high number of females may show evidence of copulationon the first morning after pairing. This is thought to be a result of forced copulation of females© 2006 by Taylor & Francis Group, LLC