Leptin expression in placental cells

J MAYMÓ; V FONTANA; JC CALVO; C VARONE

Santiago

Simposio; II Simposio latinoamericano: Interacción materno-fetal y placenta y XIX Reunión Anual de la Sociedad Chilena de Ciencias Fisiológicas; 2005

Sociedad Chilena de Ciencias Fisiológicas

Leptin, the 16 kDa protein product of the obese gene, was originally seen as an adipocyte-derived signaling molecule, but later found to be expressed in other tissues particularly in placenta. It has been suggested to be involved in some functions during pregnacy such as growth, angiogenesis and immunomodulation. The molecular mechanisms involved in the adhesion of the embryos to uterine epithelium and growth are still unknown. Recently, our group observed that, in JEG-3 and BeWo cells, recombinant leptin stimulated cell proliferation and protected placental cells from apoptosis. We also reported that IL-6, IL-1, 17b-estradiol, hCG and pregnenolone stimulated leptin secretion in placental primary cultures. Therefore, we proceeded to study the factors that could regulate leptin expression in placental cells, and this was the aim of the present investigation. Methods: JEG-3 and BeWo cells were cultured under standard conditions. Western blot analyses were carried out to detect leptin and leptin receptor proteins. Leptin promoter activity was evaluated by transient transfection with a plasmid containing different promoter regions directing the expression of the reporter gene luc. These results were normalized by the constitutive expression of the b-gal gene. Results: We observed a maximum increase in promoter activity of 8.8 and 12.9 times when cells were treated with 0.1 mM 17b-estradiol and 100 UI of hCG/ml, respectively. These effects were dose dependent and not evidenced with a promoter length of less than -1951bp. Similar results were obtained when studying endogenous leptin expression. On the other hand no significant changes were observed when cells were incubated with pregnenolone (0.1-10 mg/ml). Conclusions: All these findings put leptin as a possible link between embryo and endometrium communication and, thus, participating in the regulation of the implantation process. Supported by a grant from Universidad de Buenos Aires (UBACYT X-048).