Endometrial Stromal Polyps in Rodents: Biology, Etiology, and Relevance to Disease in Women

Abstract

Endometrial stromal polyps (ESP) are a common spontaneous reproductive tract lesion in the female rat. However, there is limited information concerning the etiology, biology, and significance of these polyps as an end point in toxicology and carcinogenicity studies. This paper reviews relevant literature to address these aspects of ESP with respect to potential relevance to human uterine tumors. Endometrial stromal polyps in rodents appear as age-related lesions. There are only a few chemicals tested for carcinogenicity in rat and mouse cancer bioassays associated with increased incidence of ESP with no common characteristics or mechanism of action. Uterine endometrial polyps that occur in women and the uterine stromal polyps that occur in rodents have distinct characteristics, although both types of uterine lesions are common, benign, and noncancerous. Human endometrial polyps develop from both endometrial and stromal components, whereas rodent polyps develop from the stromal component of the uterus. Endometrial polyps in women are hormone sensitive, but there is no scientific or experimental evidence to date that suggests that uterine stromal polyps in rodents are hormone sensitive. Therefore, based on differences in their etiology and biology, endometrial stromal polyps observed in rodent toxicity and carcinogenicity studies appear to have limited relevance to human endometrial polyps occurring in women.

Prediction of the Carcinogenic Potential of Human Pharmaceuticals Using Repeated Dose Toxicity Data and Their Pharmacological Properties

“…When we evaluate these FN substances histopathologically, 77 of the 96 FN substances appeared to induce benign tumors or benign and malignant tumors, which are considered not relevant for the human situation ( 36 ): acinar pancreatic tumors and islet cell neoplasia ( 36 ); pheochromocytomas of the adrenal medulla ( 64 ); forestomach tumors ( 65 , 66 ); hepatocellular tumors induced by peroxisome proliferators ( 48 , 67 – 69 ); fibroadenomas of the mammary gland ( 70 ); pituitary tumors (adenohypophysis tumors) ( 71 ); Leydig cell (interstitial cell) tumors of the testes ( 72 , 73 ); thyroid follicular cell tumors ( 74 – 76 ); and urinary bladder tumors ( 75 , 77 – 80 ) and uterus tumors (endometrial stromal polyps) ( 81 ). That means that 19 FN substances still remain using this approach.…”

Species and gender differences in the carcinogenic activity of trimethylolpropane triacrylate in rats and mice

“…Previous studies with B6C3F1 mice showed that TMPTA increased the relative length of estrous stages in female mice (National Toxicology Program, 2005). Although the contribution of hormones is not clearly shown in rodents, development of stromal polyps in rodents is usually associated with aging (Davis, 2012). In humans, the peak incidence of uterine sarcomas is between 50 and 65 years of age (Seddon and Davda, 2011).…”

NTP Technical Report on the Toxicology and Carcinogenesis Studies of p-Chloro-α,α,α-Trifluorotoluene (CASRN 98-56-6) in Sprague Dawley Rats (Hsd:Sprague Dawley SD) and B6C3F1/N Mice (Inhalation Studies)

“…Stromal polyps are considered a common background lesion in many strains of rats and their occurrence is thought to coincide with natural estrous cycle deregulation in rats and prolonged progesterone stimulation (Leininger and Jokinen, 1990). Conversely, others have suggested that rodent stromal polyps are not hormone sensitive (Davis, 2012). In the current study, there was evidence that exposure to p-chloro-α,α,α-trifluorotoluene for 3 months resulted in estrous cycle alterations in female rats and mice.…”