Differential Follicle Counts as a Screen for Chemically Induced Ovarian Toxicity in Mice: Results from Continuous Breeding Bioassays

Abstract

Ovaries from National Toxicology Program Reproductive Assessment by Continuous Breeding (RACB) bioassays were used to directly compare differential ovarian follicle counts and reproductive performance for 15 chemicals. Ovaries of 10 animals per group from 16 studies in CD-I .mice and 1 study each in C3H and C57BL/ 6 mice were sectioned serially at 6 /xm. Counts of small, growing, and antral follicles were obtained in every 10th section. For all follicle types, younger mice had more follicles than older mice, and CD-I mice had more follicles than age-matched animals from either inbred strain. The in-life portion of the RACB protocols demonstrated that 9 of 15 chemicals altered reproductive outcome in one or both sexes of mice, with six agents affecting females (R. E. Morrissey et al., 1989, Fundam. AppL Toxicol 13,747-777). Three of six female toxicants [2,2-bis(bromoethyl)-l,3-propanediol, BPD; ethylene glycol monomethyl ether, EGME; methoxyacetic acid, MAA] significantly decreased counts of small and/or growing follicles by 33 to 92% in CD-I mice; EGME also reduced follicle counts in the other strains. Follicle counts were decreased in progeny of animals treated with EGME or its active metabolite, MAA. For BPD, reductions in follicle numbers were proportional to dose. In CD-I mice, female toxicants di-N-hexyl phthalate, propantheline bromide, and tricresyl phosphate reduced reproductive performance but not follicle numbers. Counts were not affected by toxicants for which the susceptible sex could not be determined (bisphenol A, ethylene glycol, oxalic acid). Altered follicle counts without apparent reproductive impairment oc-' To whom correspondence should be sent at current address: Amgen,

NTP‐CERHR expert panel report on the reproductive and developmental toxicity of bisphenol A

“…Additional information on ovarian follicle counts in F 0 and F 1 females was published in a report by Bolon et al (1997). In this study, mice were fed NIH-07 open formula rodent chow and housed in polypropylene or polycarbonate cages containing Ab-Sorb-Dri litter.…”

Effects of Carbosulfan Administration Schedules on Estrous Cycle and Follicular Dynamics in Albino Mice

“…Serial sections of the ovary were evaluated for follicle stages as described by Moawad et al, 11) Pedersen and Peters 12) and Bolon et al, 13) and follicles were classified according to Chen et al,14) into small, medium and large. In the present study 3 classes of ovarian follicles were made using the relative cross sectional diameter of the follicles, as measured from the outer margins of the granulosa cell layers, the number of granulosa cell layers and the nature of the antral space.…”

Reproductive Toxicity of Carbofuran to the Female Mice: Effects on Estrous Cycle and Follicles.

“…The ovaries were fixed in Bouin's fluid, embedded in paraffin, sectioned at 5 µm thickness and stained with hematoxylin and eosin. All serial sections of the ovary were counted for various stages of development of follicles as described by Moawad et al 11) , and Bolon et al 12) . Follicles were classified according to Chen et al 13) into small medium and large follicles.…”