Leptin is a circulating hormone that is expressed abundantly and specifically in the adipose tissue. It is involved in the regulation of energy homeostasis, as well as the neuroendocrine and reproductive systems. Here, we demonstrate production of leptin by nonadipose tissue, namely, placental trophoblasts and amnion cells from uteri of pregnant women. We show that pregnant women secrete a considerable amount of leptin from the placenta into the maternal circulation as compared with nonpregnant obese women. Leptin production was also detected in a cultured human choriocarcinoma cell line, BeWo cells, and was augmented during the course of forskolin-induced differentiation of cytotrophoblasts into syncytiotrophoblasts. Plasma leptin levels were markedly elevated in patients with hydatidiform mole or choriocarcinoma and were reduced after surgical treatment or chemotherapy. Leptin is also produced by primary cultured human amnion cells and is secreted into the amniotic fluid. The present study provides evidence for leptin as a novel placenta-derived hormone in humans and suggests the physiologic and pathophysiologic significance of leptin in normal pregnancy and gestational trophoblastic neoplasms.

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.

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Abstract. Leptin is a satiety hormone secreted from the adipose tissue and human placenta. We previously demonstrated that severe preeclampsia up-regulated leptin mRNA expression in the placenta and elevated maternal plasma leptin concentrations. Preeclampsia is frequently related to generation of small for gestational age (SGA) infant especially in cases with severe preeclampsia. However, it is still controversial whether the increase in maternal plasma leptin levels is associated with fetal growth restriction without complication of preeclampsia. Therefore, the aim of the present study was to explore the relationship between maternal plasma leptin levels and fetal growth in non-preeclamptic (n = 98) and preeclamptic (n = 40) women. In non-preeclamptic pregnant women, plasma leptin levels in SGA group (n = 11) were significantly higher than those in appropriate for gestational age (AGA) group (n = 87, P<0.05). In pregnant women with preeclampsia, likewise, plasma leptin levels in SGA group (n = 15) were significantly higher than those in AGA group (n = 25, P<0.05). In multiple linear regression analysis, maternal BMI, mean arterial blood pressure and ∆SD of neonatal body weight were significant factors for determining maternal plasma leptin levels in all population studied. Maternal BMI and ∆SD of neonatal body weight showed positive correlation with maternal plasma leptin levels when analysis was performed in non-preeclamptic subjects alone. In conclusion, maternal plasma leptin levels reflect, at least partly, deterioration in fetal growth.