RESEARCH ARTICLE Compatibility of a Novel Thrombospondin-1 Analog with Fertility and Pregnancy in a Xenograft Mouse Model of Endometriosis

Endometriosis is a gynecological disease defined by the growth of endometrium outside of the uterus. Although endometriosis contributes to 50 % of female infertility cases, medical treatments are incompatible with pregnancy. Angiogenesis, the growth of blood vessels from existing vasculature, plays a crucial role in endometriotic lesion growth and survival. Previously, we demonstrated the effectiveness of thrombospondin-1 analog, ABT-898 (Ab-bott Laboratories) to inhibit endometriotic lesion vascularization in mice. We have now eval-uated the trans-generational implications of ABT-898 treatment before and during mouse pregnancy. We hypothesized that ABT-898 would target lesion vasculature without affect-ing pregnancy, offspring development, or ovarian and uterine vascularity in mice. Endome-triosis was induced using human endometrium in β-estradiol-primed BALB/c-Rag-2-/-Il2rγ-/-mice receiving intraperitoneal injections of ABT-898 (25 mg/kg) or 5 % dextrose control for 21 days. Ultrasound assessment of lesion vascularization revealed a reduction in blood flow supplying treated lesions. Excised ABT-898 treated lesions stained for CD31+ endothe-lial cells exhibited a decrease in microvessel density. Following confirmation of estrous cy-