Species: Rat Strain/breeder: Sprague-Dawley (Harlan Winkelmann, Borchen, Germany) Sex: Female Age: 3 months Study type: Repeated dose toxicity study Treatment: po (gavage), low dose Animal status: Schedulded sacrifice, end of study Clinical findings: None Organ(s): Ovaries Macroscopic finding(s): Small ovaries Staining: H&E

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Abstract

G. SCHMITZ and M. HEINRICHS

Aventis Pharma Deutschland GmbH, Drug Safety Evaluation, Toxicology/Pathology, Mainzer Landstr. 500, 65795 Hattersheim, Germany

Key words: ovotestis, rat, true hermaphroditism

True hermaphroditism is a condition, in which ovarian and testicular tissues are found in one and the same individual. In a 3-months-old Sprague Dawley rat (Hsd:Sd; Harlan-Winkelmann, Borchen, Germany), which was included as female animal in the low dose group of a 1 month toxicity study, small ovaries were evident at necropsy. Histopathologically, both ovaries were composed of ovarian as well as of testicular tissue, so called ovotestes. Vagina and uterus were normally developed, epithelium and endometrial glands of the uterine horns showed multifocal squamous cell metaplasia. Lateral to the cervix, remnants of the Wolffian duct were evident. Immunocytochemical examination of the pituitary gland revealed diffuse hyperplasia of prolactin (PRL) and luteinising hormone (LH) producing cells of the pars distalis. Reports of true hermaphroditism exist from various animal species including the rat. Although the rat as a laboratory animal species is very well examined, only few cases of spontaneous true hermaphroditism were described. The reported case here was compared to cases of true hermaphroditism found in the literature. To the best of our knowledge, 15 cases of true hermaphroditism in the rat have been reported with bilateral ovotestes present in seven rats. In five out of the seven rats with bilateral ovotestes, male as well as female genital organs were developed in one and the same animal. In one rat, only male genital organs were evident, and in one animal, genital organs were not examined. The animal reported here had bilateral ovotestes but developed only female genital organs, which led to a female phenotype.