Abstract LB248: Implantation factors assist in the growth of gynecologic tissues in ectopic locations

Abstract OBJECTIVE: Develop a model of endosalpingiosis and endometriosis to investigate the mechanisms which facilitate implantation of exfoliated cells in the peritoneum. BACKGROUND: Endosalpingiosis (ES) and endometriosis (EM) are the growth of tubal and endometrial epithelium respectively, outside of their site of origin and have been associated with ovarian cancer. Why this growth happens has not been elucidated since Sampson first proposed the concept of retrograde menstruation nearly 100 years ago. We hypothesized there is retrograde flow of uterine implantation factors which drive ectopic growth. To test this hypothesis, we developed a transgenic fluorescent murine model of ES and EM that successfully demonstrated peritoneal implantation in mice. Using the model, we explored possible influences on implantation. METHODS: tdTomato (tdT) transgenic fluorescent mice were used as donors to allow for visualization of tissues in recipient mice. A progesterone knockout (PKO) of the tdT mouse that blocks implantation factors was created by giving 0.1 mg/kg progesterone on postnatal days 2-10. Metestrus endometrium was induced hormonally in donor tdT and wild-type (WT) female C57BL/6J mice. The tdT oviductal cells and endometrium were then harvested for intraperitoneal injection into synchronized recipient WT mice, receiving minced endometrium alone, minced oviduct alone, or a combination of minced oviduct and WT endometrial tissue (for implantation factors) from non-treated or PKO tdT donors. Ectopic lesions were identified using fluorescence in-vivo imaging and UV light. RESULTS: PKO tdT oviduct had significantly reduced implantation (4 lesions/6 mice, p<0.02) compared to tdT oviduct without treatment (28 lesions/8 mice). Additionally, PKO tdT oviduct implantation (10 lesions/3 mice) may be restored when implanted with WT endometrium (p=0.07). Chi square was used to evaluate for statistical significance. ConclusionImplantation factors required for blastocyst implantation are crucial to initiate ectopic tissue growth. We have developed a novel mouse model of ectopic growth of gynecologic tissues which demonstrates that the removal of implantation factors from endometrium and oviduct reduces ectopic lesions. This model allows us to study the initial step of implantation of these lesions that could give rise to malignancies which will ultimately allow for the development of new prevention and treatment modalities. Citation Format: Jan Sunde, Derek O'Neil, Tiffany Katz, Morgan Wasickanin. Implantation factors assist in the growth of gynecologic tissues in ectopic locations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr LB248.