Platform Session 15. Diseases of the Reproductive System
Tuesday, July 26, 2005
2:00 PM–4:00 PM
Location: CCQ 202
(117) REDUCED INOSITOL PHOSPHATASE EXPRESSION DURING MEIOTIC MATURATION COINCIDES WITH THE MEIOTIC ORIGIN OF OVARIAN TERATOMAS IN A MOUSE TRANSGENE MODEL.
Chaillet, Richard1, Reinhart, Bonnie1, Ratnam, Sarayu1, 2, Ding, Feng1, 3, Eicher, Eva4, 1 University of Pittsburgh, Pittsburgh, PA2 University of Chicago, Chicago, IL3 Stanford University, Palo Alto, CA4 The Jackson Laboratory, Bar Harbor, ME
ABSTRACT- Teratomas are a unique class of tumors composed of tissues foreign to the site of origin. In humans, the most common teratoma is the ovarian teratoma, a tumor originating from a non-ovulated germ cell that initiates embryonic development. Because the parthenogenetic development is confined within the ovary, the tumor is composed of a bizarre arrangement of tissues of ectodermal, mesodermal, and endodermal origin. Very little is known about the molecular and genetic etiologies of ovarian teratomas. We are exploring the etiology of ovarian teratomas in the established Tgkd transgene mouse model. Twenty percent of hemizygous female carriers of the imprinted Tgkd transgenic line develop an ovarian teratoma. Tgkd inserted into mouse Chromosome 8 near the inositol polyphosphate 4-phosphatase (Inpp4b) gene. Normally, Inpp4b is expressed at very high levels during the meiotic maturation of fully-grown mouse oocytes with peak protein expression occurring in MII oocytes. In contrast, Inpp4b expression is diminished in MII ooctyes from Tgkd females, indicating that insertion of Tgkd disrupted Inpp4b function during oocyte development. Finally, genetic analysis indicates that ovarian teratomas in Tgkd females arise from MII ooctyes. Taken together, these findings suggest that signaling via phosphatidyl inositol metabolism prevents spontaneous egg activation in the absence of fertilization, and that phosphatidyl inositol metabolism is an important component of normal MII oocyte arrest. We suggest that a defect in signaling via phosphatidyl inositol can cause ovarian teratoma development in human females.
KEY WORDS: teratoma, oocyte, mouse, imprinting