133. LESION WEIGHT AND GLANDULAR DEVELOPMENT ARE SUPPRESSED IN A TGFB1 DEFICIENT MOUSE MODEL OF ENDOMETRIOSIS

Abstract

Endometriosis causes subfertility, pelvic pain and dysmenorrhea, and affects 10% of women of reproductive age globally. The pathology of endometriosis is still poorly understood; however microarray data from a mouse model revealed transforming growth factor beta 1 (TGFB1) as central component in molecular pathways that promote tissue remodelling of ectopic endometrial tissues [1]. We hypothesised that a host deficiency of TGFB inhibits the growth of endometriotic lesions and changes the cellular composition of the tissues. To test this hypothesis, human eutopic endometrial tissue was implanted into Tgfb1–/– mice with Tgfb1+/+ wildtype mice were used as controls (n = 8 and 19 respectively). All mice were on a background of severe combined immunodeficiency to prevent graft rejection. The weight and volume fraction of the glandular and stromal compartments of the resulting lesions were evaluated and the sections were stained with BrdU as a marker of proliferating cells. Sixty percent of mice developed ectopic endometrial lesions in both groups. The median weight of the xenografts from Tgfb1+/+ wildtype mice was 11-fold higher than the Tgfb1–/– mice (Mann-Whitney U test, P = 0.0275). The glandular volume fraction in endometriosis-like lesion from Tgfb1–/– mice was 0.35 and was 33% lower than in lesions from the control mice (volume fraction of glands = 0.52) (independent t-test, P = 0.0415). These studies show that TGFB1 is critical for normal endometriosis-like lesion development and a host deficiency of TGFB1 is associated with reduced weight and glandular volume fraction of xenografts. Targeted suppression of TGFB1 in the host response could be a successful therapeutic strategy for women with this disease.

(1) Hull ML et al., Endometrial–peritoneal interactions during endometriotic lesion establishment. Am J Pathol, 2008. 173(3): 700–715.