Abstract
Abnormal placenta trophoblast proliferation and apoptosis is related to the pathogenesis of preeclampsia. Emerging evidence has also indicated that key pregnancy-associated hormones, such as hCG, progesterone, are found in high concentration at the maternal-fetal interface. The purpose of this study was to investigate the expression of CYP11A, a key enzyme in steroid hormone synthesis and metabolism, in normal pregnancy and severe preeclampsia placenta and to explore the underlying mechanism of the relationship between the altered CYP11A expression and onset of preeclampsia. Immunohistochemistry method was used to study the localization of CYP11A-encoded protein P450scc in the placenta; reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to examine CYP11A expression at mRNA and protein levels in patients with severe preeclampsia and normal placental tissue. CYP11A overexpression in trophoblastic cells was used to evaluate the effect on viability. TUNEL staining was used to determine whether overexpression of CYP11A could affect trophoblastic cell apoptosis. The results showed that CYP11A was selectively expressed in the cytoplasm of the placental trophoblastic cells. CYP11A expression were significantly increased in severe preeclampsia compared with normal pregnancy in both mRNA and protein levels. Multiple regression analysis indicated that CYP11A gene expression was positively correlated to ALT level and Plt, while negatively correlated to INR. Overexpression of CYP11A reduced trophoblastic cell proliferation and induced HTR8/SVneo cells apoptosis through activation of activated caspase-3 expression. These results suggest that abnormally high expression of CYP11A inhibits trophoblastic proliferation and increases apoptosis and therefore could be involved in the pathogenesis of preeclampsia.
Highlights
Preeclampsia is a serious pregnancy-related complication with an incidence of approximately 5,6% in pregnant women [1]
Sample Choose Criteria All the subjects in this study attended our hospital between March 2007,May 2009 for cesarean section at gestational weeks between 35 weeks and 39 weeks. 53 cases of normal pregnancy, 37 cases of severe preeclampsia and 22 cases of mild preeclampsia were recruited for the study
The clinical data of mild, severe preeclampsia and normal pregnancy are shown in Supplemental Table S1 and S2
Summary
Preeclampsia is a serious pregnancy-related complication with an incidence of approximately 5,6% in pregnant women [1]. The etiology of preeclampsia remains poorly understood, mounting evidences have indicated that genetic factors contribute to the etiology of preeclampsia. One important characteristic of preeclampsia is that when the placenta leaves the mother, such as in the termination of pregnancy, symptoms of preeclampsia are alleviated. The exact mechanism of how the placenta factors cause symptoms of multiple organs is still poorly understood. Enguobahrie DA et al used placenta microarray to screen for preeclampsia candidate genes and suggested that some differentailly expressed genes may potentially be related to the onset of preeclampsia, such as the cholesterol side-chain cleavage enzyme gene CYP 11A)
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