Alterted SLIT2/ROBO1 signalling is linked to impaired placentation of missed and threatened miscarriage in early pregnancy

Abstract

Aims

Two-thirds of early pregnancy failures present with the reduced trophoblast invasion, and SLIT2/ROBO1 signaling is considered to play an important role in trophoblast function during pregnancy. We investigated SLIT2/ROBO1 signaling 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 β-hCG levels and shallow trophoblast invasion were observed in patients with missed and threatened miscarriage, immuohistological staining revealed abnomal Slit2 and Robo1, as well as E-cadherin and 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 cells 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

SLIT2/ROBO1 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.

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