Augmented Placental Production of Leptin in Preeclampsia: Possible Involvement of Placental Hypoxia

Abstract

Preeclampsia (PE) is a hypertensive disorder, which develops in late pregnancy and is usually associated with placental hypoxia and dysfunction. We have recently demonstrated that leptin is a novel placenta-derived hormone in humans and suggested its significance in human pregnancy (see Ref. 19). To explore the changes in the leptin production in placenta in PE, we measured the plasma leptin level and placental leptin messenger RNA expression in pregnant women with PE. Plasma leptin levels in preeclamptic women were elevated significantly, compared with gestational age- and body mass index-matched normal pregnant women (P < 0.0001). Plasma leptin levels in the severe PE group were significantly higher than those in the mild PE group (P < 0.0001). Plasma leptin levels in preeclamptic women were reduced, soon after the placental delivery, to those expected for their body mass indices. Northern blot analysis revealed that leptin messenger RNA levels are increased in the placentas from preeclamptic women, compared with normal pregnant women. Leptin secretion was increased significantly in a human trophoblastic cell line (BeWo cells) cultured under hypoxic conditions (5% O2), compared with those cultured under standard conditions (20% O2; P < 0.01). The present study demonstrated that placental production of leptin is augmented in severe PE, probably because of placental hypoxia, thereby suggesting the possible significance of leptin as a marker of placental hypoxia in severe PE.

Increased fetal leptin in Type I diabetes mellitus pregnancies complicated by chronic hypoxia

“…Our data are in agreement with the findings of another study [14] which showed that hypoxia increases placental leptin production. That study found that in vitro a rise in leptin production in placental cells did not take place until after 72 h of hypoxia [14].…”

“…That study found that in vitro a rise in leptin production in placental cells did not take place until after 72 h of hypoxia [14]. Because during hypoxic conditions a significant increase in fetal EPO concentrations can be observed within 2 to 4 h [16], the increased cord plasma leptin, together with the increased EPO concentrations in both amniotic fluid and cord plasma, probably reflect chronic or subchronic rather than acute fetoplacental hypoxia.…”

“…Both maternal glycaemic control in diabetic pregnancies and pre-eclampsia affect cord plasma leptin concentrations [13,14] and amniotic fluid and cord plasma EPO concentrations are also increased in such pregnancies [18,19,20]. Neither the number of pre-eclamptic mothers nor the maternal HbA 1C significantly differed, however, between the hypoxic and non-hypoxic group of infants.…”

“…Maternal diabetes mellitus and pre-eclampsia are also associated with increased cord blood leptin concentrations [12±14]. It has been postulated that hypoxic conditions during pre-eclampsia augment placental production of leptin [14]. Erythropoietin (EPO), which regulates the synthesis of bone marrow progenitor cells and erythrocytes [15], is produced in the fetal liver and near term also in the kidney [15].…”

Different profiles of circulating angiogenic factors and adipocytokines between early‐ and late‐onset pre‐eclampsia

“…28 Placental leptin production is elevated under hypoxic conditions, 29 and leptin levels in PE are significantly higher than in normal pregnancies, [30][31][32] suggesting that leptin derived from the placenta may play a role in the pathophysiology of PE through insulin resistance, autonomic activation or direct effects on the endothelium. Next, we investigated whether there were significant differences in adipocytokines in women with early-and late-onset PE and in healthy pregnant women.…”