title: Spontaneous metritis related to the presence of vaginal septum in pregnant Sprague Dawley Crl:CD(SD) rats: impact on reproductive toxicity studies.
abstract: Recently, 6% of 1,176 Sprague Dawley rats examined in our reproductive toxicity studies presented with dark-red uterine contents with or without fetuses demonstrating delayed development. Sometimes, a high proportion of the litter was found dead, and dystocia with death or preterminal euthanasia of the dam occurred. Microscopic findings in the uterus consisted of necrohemorrhagic and suppurative periplacentitis associated with the presence of bacterial colonies identified as Escherichia coli. In the vagina, similar findings were observed that were associated with mucus accumulation and the presence of a transverse occlusive or partially occlusive thin membrane identified as a vaginal septum. Microscopically, this septum consisted of a thin band of connective tissue covered on both sides by a mucous epithelium that was continuous with vaginal epithelium. In some cases, there was only mucus accumulation retained by a septum in the vagina without evidence of bacterial infection. Serological and histological examinations did not reveal any specific pathogenic agent. The presence of these septa in the vagina most likely favored mucus accumulation, nonspecific ascending bacterial infection, and dystocia. This colony of rats presented with an unusually high incidence of vaginal septa as it was described in different strains of mice and rats in the past. We hypothesized that the use of an impedance meter by the breeder--to determine the phase of the estrous cycle by introducing a probe in the vagina--likely facilitated gestation by perforating the vaginal septum in some cases.
authors.affiliation: sanofi-aventis R&D, Drug Safety Evaluation, Porcheville, France. Stephane.Lezmi@Covance.com
authors.forename: S
authors.initials: S
authors.lastname: Lezmi
authors.forename: K
authors.initials: K
authors.lastname: Thibault-Duprey
authors.forename: A
authors.initials: A
authors.lastname: Bidaut
authors.forename: P
authors.initials: P
authors.lastname: Hardy
authors.forename: M
authors.initials: M
authors.lastname: Pino
authors.forename: G Saint
authors.initials: GS
authors.lastname: Macary
authors.forename: S
authors.initials: S
authors.lastname: Barbellion
authors.forename: P
authors.initials: P
authors.lastname: Brunel
authors.forename: O
authors.initials: O
authors.lastname: Dorchies
authors.forename: C
authors.initials: C
authors.lastname: Clifford
authors.forename: I
authors.initials: I
authors.lastname: Leconte
mesh_terms: D000818:Animals; D005260:Female; D011247:Pregnancy; D011248:Pregnancy Complications / Q000209:etiology* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests / Q000662:veterinary; D014599:Uterus / Q000382:microbiology / Q000473:pathology*; D014621:Vagina / Q000002:abnormalities*