Siglec-6 expression is increased in placentas from pregnancies complicated by preterm preeclampsia

Abstract

Sialic acid immunoglobulin-like lectin (Siglec)-6 is a transmembrane receptor that binds sialyl-TN glycans and leptin. Among eutherian mammals, only human placentas express Siglec-6. Previous work has implicated Siglec-6 in preeclampsia (PE). Preeclampsia, a leading cause of maternal and perinatal morbidity and mortality, is characterized by placental abnormalities. This study provides a comprehensive analysis of Siglec-6 protein expression during human pregnancy by disease state (PE), biologic compartment (basal plate, chorionic villi, or maternal plasma), gestational age (24-41 weeks), and labor status. Siglec-6 protein was increased in both the basal plate and chorionic villi of preterm PE placentas (P < .05). However, expression did not differ at term by disease state, compartment, or labor status. Siglec-6 was not detectable in maternal serum. Overexpression of Siglec-6 protein in preterm PE placentas may contribute to or represent a response to PE pathogenesis and suggests that preterm PE pathogenesis is distinct from term PE.

Keywords: leptin; placenta; preeclampsia; siglec.

Figure 1.

Siglec-6 expression is increased in preterm PE placentas compared to controls. Siglec-6 expression levels were determined from immunoblots of placental tissue protein lysates (gestational age range 24-36 weeks, all from labored deliveries). Siglec-6 expression was normalized to actin expression to control for protein loading. Levels are reported as fold expression relative to a 25-week gestation sample run on all blots. Siglec-6 expression is increased in the basal plate (A) and chorionic villi (B) of preterm PE placentas (n = 11, open circles) compared to preterm labored placentas (n = 10, closed squares). (C) Sample immunoblots of Siglec-6 and actin from preterm labor and preterm PE chorionic villi are shown. Gestational age of each sample in weeks (gest wk) is indicated. The BeWO cells transfected with empty vector (negative control, −) or Siglec-6 expressing vector (positive control, +) are shown. PE indicates preeclampsia; Siglec-6, sialic acid immunoglobulin–like lectin-6.

Figure 2.

Siglec-6 expression does not change across preterm gestation in either control or PE groups. Siglec-6 expression levels were determined from immunoblots of placental tissue protein lysates (gestational age range 24-36 weeks, all from labored deliveries). Siglec-6 expression was normalized to actin expression to control for protein loading. Levels are reported as fold expression relative to a 25-week gestation sample run on all blots. Linear regression of Siglec-6 expression by gestational age showed no trend in either the basal plate (A) or chorionic villi (B) of preterm labor (n = 10, closed squares, solid line) or preterm PE samples (n = 11, open circles, dashed line). Basal plate: preterm labor, R ² = .20, P = .19, and preterm PE, R ² = .01, P = .74. Chorionic villi: preterm labor, R ² = .03, P = .61, and preterm PE, R ² = .16, P = .23. PE indicates preeclampsia; Siglec-6, sialic acid immunoglobulin–like lectin.

Figure 3.

Siglec-6 expression is unchanged in term PE placentas compared to the controls. Siglec-6 expression levels were determined from immunoblots of placental tissue protein lysates (gestational age range 37-41 weeks, all from labored deliveries). Siglec-6 expression was normalized to actin expression to control for protein loading. Fold expression is reported relative to the sample with the lowest expression. Siglec-6 expression is unchanged in the basal plate (A) and chorionic villi (B) of term PE (n = 5, open circles) and control placentas (n = 5 closed squares). PE indicates preeclampsia; Siglec-6, sialic acid immunoglobulin–like lectin-6.

Figure 4.

Siglec-6 expression is unchanged by labor at term. Siglec-6 expression levels were determined from immunoblots of placental tissue protein lysates (gestational age range 37-41 weeks). Siglec-6 expression was normalized to actin expression to control for protein loading. Fold expression is reported relative to the sample with the lowest expression. Siglec-6 expression is unchanged in the basal plate (A) and chorionic villi (B) of term labored placentas (n = 4-5, open circles, lysate from 1 basal plate labored sample was of insufficient quality for immunoblot analysis) compared to term unlabored controls (n = 5, closed squares).