Abstract
Objective: DAB2IP is a growth inhibitor present in many types of cancer cells and is associated with epigenetic regulations controlling tumor development. The primary objective of this study is to determine whether DAB2IP participates in the invasion and migration of trophoblasts during placental development.
Methods: The expressions of DAB2IP in human placentas (10 villi, 18 term placentas and 20 pre-eclampsia placentas) were determined by immunohistochemistry, Western blotting and quantitative RT-PCR. HTR8/SVneo cells were treated with hypoxia–reoxygenation (H/R) to test how DAB2IP expression would affect the invasion and migration of trophoblasts. JEG-3 andHTR8/SVneo cells were treated with 5-aza-2-deoxycytidine (5-aza-dC) to study the role of DAB2IP promoter methylation in trophoblasts.
Results: DAB2IP was strongly expressed in human villi and extravillous trophoblasts as well as in HTR8/SVneo cells, but not in pre-eclampsia placentas. DAB2IP expression increased after H/R treatment, but the invasive and migratory abilities of trophoblasts were reduced. DAB2IP expression in JEG-3 cells also increased after treatment with 5-aza-dC.
Conclusions: These findings strongly suggest that DAB2IP is an important negative regulator at the maternal–fetal interface during early pregnancy. Excessive oxidative stress can increase DAB2IP expression in trophoblasts. The mechanism of DNA methylation may involve in its function during the development of pathologic pregnancy.
Acknowledgements
Authors were grateful for the excellent technical assistance from Key Laboratory for Major Obstetric Diseases of Guangdong Province and Key Laboratory of Diagnostic Medicine designated by the Ministry of Education, Chongqing Medical University.
Declaration of interest
The authors declare that there is no conflict of interests regarding the publication of this paper. This work has been financially supported by National Natural Science Foundation of China (nos. 81070502, 81170585, 81100444, and 81370731), the funding of National Key Clinical Department in China.