Trophoblast Apoptosis and BRCA1 Expression in Fetal Growth Restriction Pregnancy

Moon, Chong Soo; Chung, Ji Youn

Abstract

OBJECTIVE
To know the role of trophoblast apoptosis and BRCA1 on pregnancy of intra-uterine fetal growth restriction (FGR). BRCA1 is regarded as not only a tumor suppressor gene but regulator of cell growth, proliferation and differentiation. We tested the hypothesis that enhanced trophoblast apoptosis and expression of BRCA1 reduced placental mass, which caused placental dysfunction and FGR.
METHODS
Placentas were obtained from women with pregnancies complicated by FGR (n=10) and from women with controlled normal pregnancies at different gestational ages (n=15). After placental sections were isolated, In Situ DNA 3'-end labelling analysis as well as detection of cytokeratin 18 cleavage products for apoptosis were measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay and counter staining with hematoxylin and eosin. The same sections were examined by means of immunohistochemistry and Western immunoblotting for identifying the expression of BRCA1 protein.
RESULTS
TUNEL staining exhibited consistently higher levels of nuclear staining and more cytokeratin 18 cleavage products in trophoblasts from FGR than normal growth pregnancy. In the trophoblasts of FGR, the BRCA1 expression and the staining intensity were more augmented on Western blotting and immunohistochemistry than normal pregnancies. There was no remarkable difference of BRCA1 expression according to gestational ages.
CONCLUSION
The expression of BRCA1 and apoptosis is up-regulated in human placental villi from pregnancies complicated by FGR. It suggests that BRCA1 may play a role in trophoblast proliferation and differentiation and be related to the pathophysiologic mechanism of FGR. We speculated that the clinical conditions associated with enhanced BRCA1-mediated apoptosis in trophoblasts and thereby contribute to placental dysfunction and FGR.