Cystic dilatation of the vaginal fornix in aged female Crj:F344/Du rats.

In the rodent, spontaneous vaginal lesions are rare. 1-3,6 No spontaneous lesions arising from the vaginal fornix in the rodent have been reported. Unexpectedly, a high incidence of cystic dilatation of the vaginal fornix was recognized in female Crj:F344/Du rats during a 2-year carcinogenicity study. To date, the cystic vaginal fornix has never been reported in the mammal, including the rodent.1-3.5,6,8 This report describes cystic dilatation of the vaginal fornix in Crj:F344/Du rats. Two hundred and fifty, 4-week-old, female Crj:F344/Du rats were purchased from Charles River Japan Inc. (Atsugi, Kanagawa, Japan). Two weeks after these rats had arrived, the animals were divided equally (50 in each group) into five groups: two control groups (untreated and vehicle [O. 1% lactose]) and three treated groups (0.01, 0.03, and 0.1% of testarticle). During a 2-year carcinogenicity study, the rats were fed powdered diet (CA1, CREA Japan Inc.) with and without the test-article and were given water ad libitum. The rats were housed five per cage, in a plastic cage with hardwood bedding and filter tops. The rats were kept at a constant room temperature of 21-25 C and a relative humidity of 50-60°/o, and the room was maintained on a 12-hour lightll2-hour dark cycle. Complete necropsies were performed both on rats dying spontaneously during the study and those euthanatized at the end of the study. More than 42 major organs including the ovary, uterus, cervix, and vagina were histologically examined on routinely hematoxylin and eosin-stained sections. During and at the end of the study, gross nodules were found in the cervix of the genital tract in 19.6% (491250) of the female F344 rats older than 667 days. As shown in Table 1, the incidence of nodules was 15.0% (1 5/100) and 22.7% (34/150) in two control and three treated groups, respectively. The occurrence of nodules in treated groups did not appear to be related to the test-article because the incidence did not increase in a dose-related fashion. In the rat, the uterus is a duplex consisting of two horns. The two uterine horns fuse at approximately the upper fourth of the cervix, but the cervical uterine canals are completely separated by the midsagittal septum shaped like the “tongue” (Fig. 1). In approximately the lower fourth of the cervix,the cervical uterus projects into the cavity of the vagina forming the “uterovaginal lips.” At this point, the vaginal fornix is between the lateral side of the projecting cervical uterus (the uterovaginal lips) and the vaginal wall (Fig. 1). The vaginal fornix is a bilateral fold forming a recess that is continuous with the cavity of the vagina. The apical portion of the midsagittal septum of the cervical uterus that projects into the cavity of the vagina through the two “lips” consists of four or five (lateral, dorsal, and ventral) lobes and may be termed as the portio vaginalis uteri (Fig. At the orifice of the vaginal fornix, the two uterine horns open into the vaginal cavity as a symmetrical, external orifice shaped in almost an “X” pattern, although a paired, separated canal is present in nearly the entire cervix. In the portio vaginalis uteri, the vaginal fornix becomes a ring-shaped fold, but its dorsocentral portion is symmetrically separated by the root of the dorsal lobe. Grossly, the nodules were usually located in the lower half of the cervix and were raised from the surface of the cervix (Fig. 2). Usually, the raised nodules were seen laterally. Of the 49 rats with nodules, 12 animals (24%) had bilateral nodules (Table 1). Thirty-seven animals (76%) had a unilateral nodule; twenty-four nodules were found on the left side and 13 on the right side in the cervix. The nodules were smooth and spherical to elongated in shape. They vaned in size, ranging from 2 x 2 x 2 to 14 x 15 x 30 mm. Nodules were green-yellow in color and in cut sections contained puslike or cheesy yellowish material. On microscopic examination, these cervical nodules proved to be the vaginal fornix, which was cystically dilated (Fig. 3). Small nodules consisted of partial, cystic dilatation of the