CXCR4, CXCR7, and CXCL12 are associated with trophoblastic cells apoptosis and linked to pathophysiology of severe preeclampsia

Abstract

Preeclampsia is a pregnancy disorder with sudden onset of maternal hypertension and proteinuria, which is characterized by defective cytotrophoblast invasion, increased apoptosis in cytotrophoblast, and diminished syncytial differentiation. In this study, samples from 11 mild preeclamptic patients, 18 severe preeclamptic patients, and 21 normal pregnant women were collected. The expression level of CXCL12 and its two receptors (CXCR4 and CXCR7) in these samples and their relationship with apoptosis were investigated. Morphological change of trophoblast cells that was observed by scanning electron microscope (SEM) indicated a significant tendency of apoptosis in the preeclamptic placenta. Immunohistochemical staining showed that expression level of three proteins was significantly lower in severe preeclamptic placentas compared with normal placentas (P<0.05), whereas no significant difference was found between mild preeclamptic and normal placentas (P>0.05). Real time quantitative PCR (RT-qPCR) and Western blot showed that both mRNA and protein expression level of CXCR4, CXCR7, and CXCL12 of trophoblasts were lower in the severe preeclampsia group than that in the normal group (P<0.05 for mRNA, P<0.01 for protein). In conclusion, our data revealed that the roles of CXCR4, CXCR7, and CXCL12 are associated with trophoblastic cells apoptosis and may be linked to the occurrence and development of severe preeclampsia.