Placental leptin: an important new growth factor in intrauterine and neonatal development?
BACKGROUND
Leptin, the protein product of the ob gene, is produced by the adipocyte and seems to function as a link between adiposity, satiety, and activity. Leptin has also been found to be necessary for pubertal development, conception, and pregnancy in mice, and is increased in prepubertal children, independent of adiposity, suggesting a role in childhood growth and development. This study investigated 100 mother/newborn pairs to determine the role of leptin in neonatal development. Placental tissue was assayed for leptin mRNA to evaluate it as a source of leptin production in utero.


METHODS
One hundred mother/newborn pairs were enrolled in this study. Radioimmunoassay was performed for leptin on maternal venous and newborn cord blood. Leptin concentrations were measured in 43 children in Tanner stages 1 and 2 as a control group. Placental tissue was obtained from five mothers and assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR). Human placental cell lines JAR and JEG-3 were also assayed for leptin mRNA expression.


RESULTS
Leptin was present in all newborns studied at a mean concentration of 8.8 ng/mL (+/-9.6 standard deviations). Leptin concentrations in cord blood correlated with newborn weight (r = .51), body mass index (BMI) (r = .48), and arm fat (r = .42). There was no correlation between leptin and insulin. When statistically covarying for adiposity for newborns and Tanner stages 1 and 2 children, newborns had greater concentrations of leptin (mean, 10.57 ng/mL) than children (mean, 3.04 ng/mL). Leptin was present in all mothers at a mean value of 28.8 ng/mL (+/-22.2 standard deviations). Leptin concentration correlated with prepregnancy BMI (r = .56), BMI at time of delivery (r = .74), and arm fat (r = .73). Maternal leptin correlated with serum insulin (r = .49). There was no correlation between maternal and newborn leptin concentrations. Thirteen percent of newborns had higher leptin concentrations than their mothers. Placental tissue from five separate placentas expressed leptin mRNA at comparable or greater levels than adipose tissue. Two human trophoblastic placental cell lines, JAR and JEG-3, also expressed leptin mRNA.


CONCLUSIONS
The correlation between leptin and adiposity found in children and adults was also found in newborns. Serum leptin concentrations in newborns were increased more than three-fold compared with children in Tanner stages 1 and 2 when controlling for adiposity, suggesting that leptin concentrations in the newborn are not explained by adiposity alone. Maternal leptin concentrations correlated with measures of adiposity at delivery but did not correlate with newborn adiposity or leptin. Leptin mRNA was expressed both in placental tissue and in two human placental cell lines. These data suggest that leptin has a role in intrauterine and neonatal development and that the placenta provides a source of leptin for the growing fetus.
Hassink
S G
SG
Department of Pediatrics, Alfred I. duPont Institute, Wilmington, DE 19803, USA.
de Lancey
E
E
Sheslow
D V
DV
Smith-Kirwin
S M
SM
O'Connor
D M
DM
Considine
R V
RV
Opentanova
I
I
Dostal
K
K
Spear
M L
ML
Leef
K
K
Ash
M
M
Spitzer
A R
AR
Funanage
V L
VL
D000273:Adipose Tissue / Q000033:anatomy & histology / Q000378:metabolism; D000328:Adult; D000367:Age Factors; D000886:Anthropometry; D001706:Biopsy; D015992:Body Mass Index; D002478:Cells, Cultured / Q000378:metabolism; D002648:Child; D002657:Child Development / Q000502:physiology*; D018076:DNA, Complementary / Q000032:analysis; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005163:Factor Analysis, Statistical; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn / Q000502:physiology*; D007328:Insulin / Q000097:blood; D020738:Leptin; D008297:Male; D009765:Obesity / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D010920:Placenta / Q000737:chemistry*; D016133:Polymerase Chain Reaction; D011247:Pregnancy / Q000502:physiology*; D011506:Proteins / Q000032:analysis* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D012727:Sex Characteristics
D018076:DNA, Complementary; D007328:Insulin; D020738:Leptin; D011506:Proteins; D012333:RNA, Messenger