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Alterted SLIT2/ROBO1 signalling is linked to impaired placentation of missed and threatened miscarriage in early pregnancy
Author(s) -
Li Ping,
Shi Yuxun,
Shuai Hanlin,
Cai Yanzhen,
Lu Wenhui,
Wang Guang,
Gao Lufen,
Wang Lijing,
Fan Xiujun,
Yang Xuesong
Publication year - 2017
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/his.13250
Subject(s) - trophoblast , miscarriage , decidua , placentation , angiogenesis , placenta , biology , chorionic villi , pregnancy , recurrent miscarriage , andrology , cancer research , medicine , microbiology and biotechnology , fetus , genetics
Aims Two‐thirds of early pregnancy failures present with reduced trophoblast invasion, and SLIT 2/ ROBO 1 signalling is considered to play an important role in trophoblast function during pregnancy. We investigated SLIT 2/ ROBO 1 signalling associated with missed and threatened miscarriage during early gestation. Methods and results Human placenta samples were collected from women with missed miscarriage ( n = 25), threatened miscarriage ( n = 22) and termination of pregnancy controls ( n = 32). Corresponding decreases in beta human chorionic gonadotrophin (β‐hCG) levels and shallow trophoblast invasion were observed in patients with missed and threatened miscarriage, immunohistological staining revealed abnormal Slit2 and Robo1, as well as E‐cadherin and activating protein‐2 alpha (AP‐2α) expression in villi and extravillous trophoblasts, and the expression of these proteins were confirmed in villi and decidua of miscarriage material by Western blotting. Using HTR8/SVneo cells, blocking SLIT2/ROBO1 signalling promoted cell migration, proliferation and suppressed differentiation. Moreover, blocking SLIT2/ROBO1 signalling in HTR8/SVneo cells altered trophoblast differentiation‐related and angiogenesis‐related gene mRNA expression, which also occurred in the tissues of missed and threatened miscarriage. Conclusions SLIT 2/ ROBO 1 signalling may regulate trophoblast differentiation and invasion causing restricting β‐ hCG production, shallow trophoblast invasion and inhibiting placental angiogenesis in missed and threatened miscarriage during the first trimester.