Trophoblast expression of the minor histocompatibility antigen HA-1 is regulated by oxygen and is increased in placentas from preeclamptic women.

INTRODUCTION: Maternal T-cells reactive towards paternally inherited fetal minor histocompatibility antigens are expanded during pregnancy. Placental trophoblast cells express at least four fetal antigens, including human minor histocompatibility antigen 1 (HA-1). We investigated oxygen as a potential regulator of HA-1 and whether HA-1 expression is altered in preeclamptic placentas. METHODS: Expression and regulation of HA-1 mRNA and protein were examined by qRT-PCR and immunohistochemistry, using first, second, and third trimester placentas, first trimester placental explant cultures, and term purified cytotrophoblast cells. Low oxygen conditions were achieved by varying ambient oxygen, and were mimicked using cobalt chloride. HA-1 mRNA and protein expression levels were evaluated in preeclamptic and control placentas. RESULTS: HA-1 protein expression was higher in the syncytiotrophoblast of first trimester as compared to second trimester and term placentas (P<0.01). HA-1 mRNA was increased in cobalt chloride-treated placental explants and purified cytotrophoblast cells (P = 0.04 and P<0.01, respectively) and in purified cytotrophoblast cells cultured under 2% as compared to 8% and 21% oxygen (P<0.01). HA-1 mRNA expression in preeclamptic vs. control placentas was increased 3.3-fold (P = 0.015). HA-1 protein expression was increased in syncytial nuclear aggregates and the syncytiotrophoblast of preeclamptic vs. control placentas (P = 0.02 and 0.03, respectively). DISCUSSION: Placental HA-1 expression is regulated by oxygen and is increased in the syncytial nuclear aggregates and syncytiotrophoblast of preeclamptic as compared to control placentas. Increased HA-1 expression, combined with increased preeclamptic syncytiotrophoblast deportation, provides a novel potential mechanism for exposure of the maternal immune system to increased fetal antigenic load during preeclampsia.

Role of ultrasound in pre-eclampsia.

Pre-eclampsia (PE), defined as de novo hypertension (>140/90 mmHg) appearing after 20 weeks of gestation accompanied by proteinuria (>0.3 g/24 h), remains a major source of perinatal growth restriction, prematurity and death worldwide. Since its introduction practitioners have increasingly utilized fetal ultrasonography for the management of pre-eclampsia. Ultrasonographic diagnostic modalities including fetal biometric growth curves, the biophysical profile and umbilical artery Doppler have been used to detect fetal growth restriction and assess fetal wellbeing, respectively. Doppler studies of the middle cerebral and uterine arteries offer additional utility in the prediction of adverse pregnancy outcomes and as a potential screening test for pre-eclampsia. The purpose of this review was to explore the developments of ultrasound technology that have been relevant to the screening, diagnosis and management of pre-eclampsia.