238. Endometrial vessel morphology is altered following progestin treatment in a mouse xenograft model

Abstract

Human endometrium undergoes cyclic changes under the influence of oestrogen and progesterone. When progestins are used for contraception, the endometrium regresses and breakthrough bleeding often occurs. The aim of this study was to investigate the short-term effects of progestin on human endometrium in a mouse xenograft model. Uterine tissue was placed subcutaneously into NOD/SCID mice (n = 12). Mice were given estradial valerate every fourth day for two weeks. Mice then received an implant containing medroxyprogesterone acetate (MPA) or an empty implant. After two weeks, mice were dissected and the xenografts formalin fixed and serially sectioned (5µm) for immunohistochemical analysis. Sections were double immunostained for α-smooth muscle actin and either FVIII (blood vessels) or D2–40 (lymphatic vessels). The endometrium from the progestin treated group contained decidual-like stroma cells and glandular epithelium with morphology ranging from squamous to columnar. The endometrium from the control group also contained fibroblast-like stromal cells and glandular epithelium with tall columnar epithelium. The endometrial blood vessel density was significantly reduced in the progestin-treated group (156.3 ± 13.4 vessel profiles/mm²) compared with the control group (273.5 ± 41.5 vessel profiles/mm²) (P = 0.02); there was no significant difference in lymphatic vessel density (progestin: 43.5 ± 5.9 v. control: 35.6 ± 9.6 vessel profiles/mm²). Blood vessel area was significantly increased in the progestin-treated group (3.7x10⁻⁴ ± 1.7x10⁻⁵ mm²) compared with controls (1.8x10⁻⁴ ± 1.2x10⁻⁵ mm²) (P = 0.0001) and the lymphatic v essel area was also significantly increased in the progestin-treated group (8.8x10⁻⁴ ± 7.8x10⁻⁵ mm²) compared with controls (2.9x10⁻⁴ ± 5.7x10⁻⁵ mm²) (P = 0.0001). This work has provided a model for the study of human endometrial vasculature, illustrating a significant increase in blood and lymphatic vessel size during progestin treatment. The increase in blood vessel size was associated with a significant reduction in blood vessel density in progestin treated samples.