Much of the work carried out by DTT is in support of the National Toxicology Program (NTP), an interagency partnership of the Food and Drug Administration, National Institute for Occupational Safety and Health, and NIEHS.
Molecular Pathogenesis Group
One animal model of human uterine disease that we've assessed is diethylstilbestrol (DES)-induced uterine leiomyomas. In the past, the focus has been mainly on DES-induced epithelial lesions, particularly vaginal adenosis and adenocarcinoma; however, uterine smooth muscle cells are also recognized as cellular targets of DES.
We have found uterine leiomyomas that occur in mice following exposure to DES prenatally on days 9-16 of gestation or on neonatal days 1-5. These DES-induced leiomyomas have typical gross and histomorphologic characteristics of spontaneously occurring smooth muscle tumors of B6C3F1 mice previously described in our laboratory, and they are also similar to those observed in women.
- Newbold RR, Moore AB, and Dixon D. (2002). Characterization of uterine leiomyomas in CD-1 mice following developmental exposure to diethylstilbestrol (DES). Toxicol Pathol 30(5): 611-616. [Abstract Newbold RR, Moore AB, and Dixon D. (2002). Characterization of uterine leiomyomas in CD-1 mice following developmental exposure to diethylstilbestrol (DES). Toxicol Pathol 30(5): 611-616.]
We are also assessing the utility of the potbellied pig as a model for spontaneously occurring uterine leiomyomas. Unlike commercially-raised hogs, potbellied pigs provide an aging population, with the life span estimated to be as long as 20-25 years, with an average of 10-15 years. Many female pet pigs are neither spayed nor bred. As a result, intact potbellied pig females are subject to cyclic hormonal influences about every 21 days, somewhat approximating the year-round cyclic hormonal influences of the menstrual cycle in women.
- Mozzachio K, Linder K, and Dixon D. (2004). Uterine smooth muscle tumors in potbellied pigs (Sus scrofa) resemble human fibroids: a potential animal model. Toxicol Pathol 32(4):402-7. [Abstract Mozzachio K, Linder K, and Dixon D. (2004). Uterine smooth muscle tumors in potbellied pigs (Sus scrofa) resemble human fibroids: a potential animal model. Toxicol Pathol 32(4):402-7.]
The potbellied pig appears to have a high incidence of spontaneous uterine leiomyomas, previously unrecognized due to the low density and scattered distribution of pet pigs. Studies are underway to understand the biological relevance of these tumors to fibroids found in women.