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


METHODS
The 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).


RESULTS
Marked 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.


CONCLUSIONS
The 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.
Department of Nursing Science, Jinan University, Guangzhou 510632, China; Key Laboratory for Regenerative Medicine of the Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China.
Ping
P
Li
Department of Pathology, Guangdong Provincial Hospital of TCM, Guangzhou 510120, China.
Hui
H
Peng
Key Laboratory for Regenerative Medicine of the Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China.
Wen-Hui
WH
Lu
Department of Gynecology & Obstetrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
Han-Lin
HL
Shuai
Department of Gynecology & Obstetrics, The First Affiliated Hospital, Jinan University, Guangzhou 510630, China.
Qing-Bin
QB
Zha
Key Laboratory for Regenerative Medicine of the Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China; Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
Cheung-Kwan
CK
Yeung
Key Laboratory for Regenerative Medicine of the Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China.
He
H
Li
Institute of Vascular Biological Science, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Li-Jing
LJ
Wang
Stem Cell and Regeneration Thematic Research Programme, School of Biomedical Sciences, Chinese University of Hong Kong, Shatin, Hong Kong.
Kenneth Ka
KK
Ho Lee
Department of Developmental and Regenerative Biology, College of Life Science and Technology, Jinan University, Guangzhou 510632, China. Electronic address: tzhuwj@jnu.edu.cn.
Wei-Jie
WJ
Zhu
Key Laboratory for Regenerative Medicine of the Ministry of Education, Department of Histology and Embryology, School of Medicine, Jinan University, Guangzhou 510632, China. Electronic address: yang_xuesong@126.com.
Xuesong
X
Yang
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition; D005187:Fallopian Tubes / Q000473:pathology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011247:Pregnancy; D011274:Pregnancy, Tubal / Q000378:metabolism* / Q000473:pathology; D011971:Receptors, Immunologic / Q000378:metabolism*; D014327:Trophoblasts / Q000502:physiology*; D066253:Vascular Remodeling; D014746:Vimentin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
D015820:Cadherins; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D011971:Receptors, Immunologic; D014746:Vimentin; D051176:beta Catenin; D000097905:Roundabout Proteins; D000098552:Slit Homolog 2 Protein
Extravillous trophoblast; Slit2/Robo1; Tubal pregnancy; Vascular remodeling