Leptin withdrawal after birth: a neglected factor account for cognitive deficit in offspring of GDM mother

Pregnancy in the diabetic woman has long been associated with an increased risk of cognitive deficit in the offspring, which might be associated with the poor intrauterine environment for the developing fetal brain. Leptin, as an important hormone regulating the intrauterine and early extrauterine life growth and development, greatly elevated during diabetic pregnancy. The current results indicate that leptin exerts neurotrophic actions during the critical period of development of hippocampus, and acts as a cognitive enhancer. Leptin resistance was a common phenomenon in diabetic pregnancies resulting reduced leptin receptors and signaling. With sudden withdrawal of placenta-derived leptin after birth, neonatal leptin levels declined sharply. The declined leptin could not work normally with the reduced leptin receptor and thus affected the newborn's brain development, which at least partly accounted for later cognitive deficits of offspring of GDM mother. Our hypothesis provides an alternative strategy to decrease the risk of cognitive deficit of offspring of diabetic mother, by exogenously supplementing leptin after birth for some period.