STP Position Paper: Ovarian Follicular Counting in the Assessment of Rodent Reproductive Toxicity

Evaluation of the ovary is an important endpoint in tox-icological assessments because xenobiotics that cause lossof oogonia, oocytes, or supportive somatic cells may haveadverse effects on reproduction. To make an adequate histo-logic assessment of the ovary, knowledge of all morphologiccomponents and an understanding of the changes that occurduring the normal estrous cycle and aging are required. Athorough,qualitativelightmicroscopicexaminationbyatox-icologic pathologist will detect morphologic features associ-atedwithmostfunctionalalterations,includingchangesintherelative number or density of ovarian components. Develop-ment of consistent, reliable, and cost-effective quantitativemethods to evaluate ovarian toxicity has been challenging.Much effort has been spent developing adequate methods forquantification of small follicles. The publications by Bolonetal.(1997)andBuccietal.(1997)providethemostthoroughrecent comparisons of follicle-counting techniques in mice.These follicular-counting methods have been adopted and/ormodified for use as first-tier screening methods in some reg-ulatory guidelines for reproductive toxicity studies.