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

Abstract

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 Placenta 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.

Preliminary RNA-Seq Analysis of Long Non-Coding RNAs Expressed in Human Term Placenta

“…Rho GTPases are engaged in the proper functioning of the endothelial barrier [ 64 ], embryogenesis [ 65 ], neural development [ 66 ], cytokinesis, and differentiation [ 67 ]. ArhGAP45 mRNA expression is elevated in preeclamptic placentas and is under the control of oxygen accessibility [ 68 ]. GATA binding protein 2 ( GATA2 ) regulates stage-specific trophoblastic gene expression of the preimplantation human embryo [ 69 , 70 , 71 ].…”

The role of maternal T cell and macrophage activation in preterm birth: Cause or consequence?

“…However, other pregnancy abnormalities may be associated with a female infant. The expression of other minor antigens in trophoblast raise the possibility of generation of other anti-fetal responses that might play a role in abnormal pregnancy [140]. In humans, minor antigens related to abnormal pregnancy may be presented in the context of HLA-C [90].…”

Trophoblast Glycoprotein (TPGB/5T4) in Human Placenta: Expression, Regulation, and Presence in Extracellular Microvesicles and Exosomes

“…Detailed clinical characteristics of PE and matched control placental samples have been described by Linscheid et al 30 Patients did not differ in maternal age, body mass index (BMI), or gestational age at delivery; infant birth weight was significantly lower for patients with PE (1930 + 210 g vs 2514 + 141 g; mean + SEM for PE and controls, respectively; P < .001). Other samples were collected at term (>37 weeks gestation) from uncomplicated Cesarean deliveries without labor; clinical information for 5 specimens is available; average gestation age was 39.23 + 0.04 weeks; maternal BMI, 32.1 + 0.99, and infant birth weight 3664 + 80.5 g.…”