Apparent Mesonephric Duct (Rete Anlage) Origin for Cysts and Proliferative Epithelial Lesions in the Mouse Ovary

Abstract

Ovaries and adjacent parovarian (mesovarial) tissues of CD-1 mice of various ages were examined to characterize cystic and proliferative epithelial lesions of the ovary and parovarian tissues. Ovaries and adjacent tissues from 6 mice each at approximately 3 and 8 months of age were processed for light microscopy and step-sections (50-l intervals) of the entire tissue were examined. Tissues were collected from 40 mice each at 16 through 24 months of age and 3 step sections per mouse were examined. Mesonephri c duct remnants were found in all mice at 3 and 8 months. Ducts were usually in the mesovarial adipose tissue and near or within the ovarian hilus and were often loosely associated with smooth muscle of the mesovarial ligament. The epithelium of the ducts varied from low cuboidal to columnar, occasional individual cells were ciliated, and small papillary con gurations of epithelium were occasionally present. Ducts were dilated ( > 1 mm) more often in mice at 8 months compared to 3 months, and some were continuous with cystic spaces within the ovaries. As mice aged (16-24 months), dilation and cystic change in ducts and associated compression of ovarian tissue away from the ovarian hilus became common. The epithelium of dilated ducts was generally attened, but foci of cuboidal to columnar epithelium and/or occasional ciliated cells were present. Many ducts contained foci of hyperplastic and/or hypertrophic epithelium, and papillary projections of epithelium were occasionally found. Some of the latter lesions were consistent with a diagnosis of papillary cystadenoma. Hyperplasia of associated bromuscular stroma was limited to a few apparently extraovarian ducts. The results of this study indicate that remnant mesonephric ductular structures are common in and adjacent to the ovaries of CD-1 mice. As mice age, these ducts become dilated and, in some, the epithelium becomes hyperplastic and /or hyperptrophic . These mesonephri c duct remnants appear to be a common source of ovarian and parovarian cyts cysts and epithelial neoplasms of the ovary in mice.

E-cadherin expression and bromodeoxyuridine incorporation during development of ovarian inclusion cysts in age-matched breeder and incessantly ovulated CD-1 mice

“…Dilation of the rete ovarii with age has been noted previously in CD-1 (Swiss Webster) mice [2,19] and appears to be a feature of this outbred strain, since similar cysts are not found in 12-month virgin or breeder inbred C57/BL6 or 9-month outbred Quackenbush mice (J. S. Fleming, unpublished observations). Recent studies by Clark-Knowles and colleagues showed conditional knockout of the Brca1 gene in the OSE of FVB mice, led to an increase in preneoplastic changes in ovarian biology, including OSE invagination, epithelial cell hyperplasia and small inclusion cysts, but did not give rise to ovarian cancers, up to 8 months after inactivation of Brca1 in the OSE [20].…”

The transcription factor GATA4 is required for follicular development and normal ovarian function

“…9E, F), consistent with the epithelial origin of these cells. Unlike OSE, which is devoid of cilia, cells of the ovarian rete epithelium expose multiple motile cilia on their apical surfaces (Long, 2002; Tan et al, 2005). Staining for acetylated α-tubulin, a well-known marker of the ciliary axoneme, demonstrated that epithelial cells underlying the ovarian cysts in mutant ovaries expressed cilia on their apical surface (Fig.…”

Derivation of a Bisphenol a Oral Reference Dose (RfD) and Drinking-Water Equivalent Concentration∗

“…While there was an apparent treatment-related increase in paraovarian cysts in CD-1 mice fed BPA compared to the concurrent controls, Tyl et al (2007) indicated that response should be discounted due to the pathogenesis of the particular lesion in aging mice and the incidence in historical controls (Long, 2002). If biologically relevant, this lowest BMDL 10 is 15-fold higher than the 5-mg/kg-d NOAEL based on changes in liver histology associated with chronic BPA ingestion (Tyl et al, 2007).…”