title: Influence of sampling on the reproducibility of ovarian follicle counts in mouse toxicity studies.
abstract: Different ovarian follicle counting procedures were investigated to reduce labor while retaining statistical power. Intact ovaries of untreated CD-1 mice (20/group) from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) studies were serially sectioned at 6 microm. Mean numbers of small and growing follicles were used to assess sampling efficiency. In 10 mice per group, comparisons were made between 10% nonrandom samples from every 10th section starting at either the first or sixth section having follicles (approximately 40 sections per ovary). These 10% counts were compared with 5% (20 sections) and 20% (80 sections) nonrandom samples and with 1% (4 sections), 5%, or 10% random samples from the same 10 animals. For two studies, a 10% nonrandom sample was analyzed from 20 mice per group. Follicle counts for each group were comparable regardless of the sampling paradigm. Four to 10 animals provided 90% confidence that a 20% difference in mean counts would be detected. The 1% sample had a larger error term and, thus, slightly reduced statistical power. These data suggest that follicle counts from 1% or 5% random samples may provide a suitable screen for ovarian toxicity.
authors.affiliation: Pathology Associates International (an SAIC Company), National Center for Toxicological Research, Jefferson, Arkansas 72079, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Bucci
authors.forename: B
authors.initials: B
authors.lastname: Bolon
authors.forename: A R
authors.initials: AR
authors.lastname: Warbritton
authors.forename: J J
authors.initials: JJ
authors.lastname: Chen
authors.forename: J J
authors.initials: JJ
authors.lastname: Heindel
mesh_terms: D000818:Animals; D002452:Cell Count / Q000379:methods; D003627:Data Interpretation, Statistical; D005260:Female; D006652:Histological Techniques; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D006080:Ovarian Follicle / Q000166:cytology*; D011897:Random Allocation; D015203:Reproducibility of Results; D012107:Research Design