“Leptin enhances cell proliferation and survival in placental cells”

FEDERICO IBARBALZ; JULIETA MAYMÓ; YÉSICA GAMBINO; JUAN CARLOS CALVO; BERNARDO MASKIN; CECILIA VARONE

Santiago de Chile

Congreso; International Federation of Placenta Associations (IFPA); 2010

IFPA

Fetal-maternal dialogue during implantation involves multiple regulators such as leptin. This 16KD protein plays diverse roles in placental growth and survival. Previous results from our group demonstrated that leptin increases cell proliferation and survival in JEG-3 and BeWo cells. We also demonstrated that leptin expression is tightly regulated by different placental regulators. The aim of the present work is to study the mechanisms involved in placental proliferation and apoptosis. Methods: BeWo, JEG-3 and Swan cells, and human term placental explants were used. Western blot analyses were carried out to detect leptin, Bcl-2, Bax and p53 expression. Cell proliferation was determined by cell counting and 3H-thymidine incorporation. Transfection assays with reporter constructs were used to determine leptin effect on different transduction pathways. Results: Leptin treatment in Swan cells increased cell proliferation up to 3 times. Maximal effect was achieved with 100 ng leptin/ml at two days of incubation. Caspase-3 activation was determined by Western blot. Leptin diminished the proteolysis of caspase-3 in a dose dependent manner. Moreover the diminution in endogenous leptin by treatment with an antisense oligonucleotide (2-4 ìM) increases cellular apoptosis measured by caspase-3 activation. Bcl-2 and Bax levels were determined after leptin treatment and the relationship between them calculated. The expression of the key cell cycle regulator p53 was also determined. Slightly changes were observed Conclusions: All these results reinforce the notion of leptin as a placental cytokine with the function of promote growth and survival of placental cells.