Involvement of leptin in the molecular physiology of the placenta

SCHANTON, MALENA; MAYMÓ, JULIETA LORENA; PÉREZ-PÉREZ, ANTONIO; SANCHEZ-MARGALET, VICTOR; VARONE, CECILIA

REPRODUCTION

BIOSCIENTIFICA LTD

Año: 2018 vol. 155 p. 1 - 12

1470-1626

Leptin is a homeostatic regulator in the placenta where it promotes proliferation, protein synthesis and the expression of tolerogenicmaternal response molecules such as HLA-G. Leptin also exerts an anti-apoptotic action in placenta controlling the expression of p53master cell cycle regulator under different stress conditions. On the other hand, leptin is an integrative target of different placentalstimuli. The expression of leptin in placenta is regulated by hCG, insulin, steroids, hypoxia and many other growth hormones,suggesting that it might have an important endocrine function in the trophoblastic cells. The leptin expression is induced involvingthe cAMP/PKA or cAMP/Epac pathways which have profound actions upon human trophoblast function. The activation of PI3K andMAPK pathways also participates in the leptin expression. Estrogens play a central role during pregnancy, particularly 17β-estradiolupregulates the leptin expression in placental cells through genomic and non-genomic actions. The leptin promoter analysis revealsspecific elements that are active in placental cells. The transcription factors CREB, AP1, Sp1, NFκB and the coactivator CBP areinvolved in the placental leptin expression. Moreover, placental leptin promoter is a target of epigenetic marks such as DNAmethylation and histone acetylation that regulates not only the leptin expression in placenta during pregnancy but also determinesthe predisposition of acquiring adult metabolism diseases. Taken together, all these results allow a better understanding of leptinfunction and regulatory mechanisms of leptin expression in human placental trophoblasts, and support the importance of leptinduring pregnancy and in programming adult health.