Congenital uterine wall
cysts arising from paramesonephric (Müllerian) and mesonephric (Wolffian) ducts are typically incidental findings in most species. We used immunohistochemistry to characterize and determine the origin of uterine
cysts in Sprague-Dawley (SD) rats from multigeneration studies conducted by the National Toxicology Program. Subserosal uterine
cysts were observed in 20 of the 2,400 SD rats evaluated in five studies, and 10
cysts were characterized for this study. Single
cysts were unilocular, fluid-filled, and occurred throughout the uterus. Microscopically, all
cysts had a well-developed smooth muscle wall, lined by flattened to cuboidal, sometimes ciliated, epithelium that stained intensely positive for
cytokeratin 18 and paired box
protein 8 (PAX8). Most
cyst epithelia displayed weak to moderate positivity for
progesterone receptor (PR) and/or
estrogen receptor α (ER-α), as well as were negative for GATA
binding protein 3 (GATA3).
Cyst lumens contained basophilic flocculent material. The
cysts appeared to be developmental anomalies arising from paramesonephric tissue based on positive PAX8 and ER-α and/or PR staining. Additionally, 70% of the
cysts lacked GATA3 expression. Taken together, the subserosal uterine
cysts observed in adult rats in these studies most likely arose from the paramesonephric duct.