Role of Slit2/Robo1 in trophoblast invasion and vascular remodeling during ectopic tubal pregnancy

• Trophoblast – vascular cell interaction in ectopic tubal pregnancy occurs in the same fashion as in intrauterine pregnancy.
• Both stellate-shaped EVTs and polygonal-shaped EVTs are observed in the invading processes.
• Expression of Slit2 and Robo1 varies in relate to trophoblasts phenotype and remodeling stage of vessels.
• Slit2 affects the development of vasculature in the labyrinth zone of mice.

IntroductionFor ectopic tubal pregnancy to be viable, it requires a supporting vascular network and functioning trophoblast. Slit2/Robo1 signaling plays an important role in placental angiogenesis during normal pregnancy. Hence, we here investigated whether or not Slit2/Robo1 signaling also had an impact in ectopic tubal pregnancy.MethodsThe Slit2 and Robo1 expression pattern relevant to trophoblast invasive behavior and vascular remodeling was studied in human tubal placenta obtained from patients with ectopic pregnancy (5–8weeks gestation), The trophoblast development, vascular architecture and Robo1 expression pattern were observed in Slit2 overexpression (Slit2-Tg) and C57BL mice placenta (E13.5 and E15.5).ResultsMarked with CK-7 and Vimentin, the vessel profiles of fallopian tube were classified into four stages. In the presence of extravillous trophoblast (EVT), stellate-shaped and polygonal-shaped EVTs were observed, and the stellate-shaped EVT showed the higher Slit2 expression (P < 0.01) but lower Robo1 expression (P < 0.05) than polygonal-shaped cells. By contrast, a temporary Slit2 up-regulation in remodeling vessel and Slit2 down-regulation in remodeled vessel of polygonal-shape extravillous trophoblast cells occurred in tubal pregnancies. In Slit2-Tg mice E13.5 and E15.5 placenta, Slit2 overexpression promoted vascular remodeling by increasing in the diameter of the maternal blood sinusoids and fetal capillaries, but enhanced the thickness of trophoblast and vasculature at E15.5 Slit2-Tg mice.ConclusionsThe varying Slit2 and Robo1 expression in EVTs was associated with trophoblast invasion and probably plays an important role in the events of blood vessel remodeling of the fallopian tube tissues.