Does LIN28B gene dysregulation make women more likely to abort?

Abstract

Background: LIN28B plays an important role in early embryonic development, but its role in villous trophoblast implantation and differentiation remains unknown. This study aims to verify the role of LIN28B in trophoblastic villous tissue and cells from women with URSA (unexplained recurrent spontaneous abortion) and artificial termination of pregnancy (negative control, NC).

Methods: The LIN28B gene and its protein expression level were detected with real-time quantitative PCR, Western immunoblotting analysis, and immunocytochemistry. The gene was also overexpressed in chorionic villous cell lines (HTR-8/SVneo and BeWo) to examine its effect on trophoblast function.

Results: The expression of LIN28B mRNA and protein of URSA villi was lower than that in the NC group. At the cellular level, overexpression of LIN28B enhanced cellular migration, and invasion, and inhibited apoptosis. LIN28B may inhibit apoptosis by promoting Akt phosphorylation and by inhibiting Bad phosphorylation and Bcl-2 expression. In addition, LIN28B inhibited cell fusion and reduced cellular syncytia.

Conclusions: LIN28B can inhibit cell invasion and migration in vitro and promote apoptosis and fusion. The low expression of LIN28B in URSA villous trophoblast cells may be one of the causes of abortion. The role of LIN28B in villous trophoblasts needs further study.

Lay summary: Propagation of offspring is of great significance to the continuation of the human race. However, continuous pregnancy is more difficult for some women, especially women who have multiple miscarriages. One important contributor is the cessation of development caused by genetic factors of the embryo, but there are still many unknown reasons. We investigated the LIN28B gene which is a possible pathogenic factor in the placenta. We collected 25 cases of abortion in the experimental group (unexplained recurrent abortion group) and 25 in the control group (artificial termination of pregnancy group): on average at 7-8 weeks of pregnancy. We tested the function of lin28b in these samples and verified its function in cell lines. LIN28B plays an important role in maintaining early pregnancy by promoting the invasion of villous cells, inhibiting apoptosis and fusion, and the reduction of LIN28B expression may lead to the occurrence of early miscarriage.