Leptin-directed embryo implantation: Leptin regulates adhesion and outgrowth of mouse blastocysts and receptivity of endometrial epithelial cells

Abstract

Leptin is a 16-kDa multifunctional protein. Recent reports indicate that leptin is an important molecule during implantation and placentation, implicated in embryonic-maternal cross-talk and cytotrophoblast invasiveness, however, the role of leptin playing in the process of normal blastocyst implantation has not been well characterized. In the present study, the possible mechanisms of leptin playing in mouse blastocyst implantation were investigated. Leptin and receptor isoforms mRNAs were detected in whole mouse uteri during estrous cycle and peri-implantation periods. Immunofluorescent analysis further confirmed Ob-R protein was present in mouse uterus. The differential amounts of leptin and Ob-R isoforms suggested a role for leptin in such endometrial issues as blastocyst implantation. In vitro culture model for studying embryo implantation, leptin promoted mouse blastocyst adhesion and blastocyst outgrowth on fibronectin. Blastocysts treated with 300 ng/ml leptin had the greatest adhesion rate of 76.58 ± 6.41% ( P = 0.046), and blastocysts treated with 30 ng/ml leptin had the greatest outgrowth rate of 78.64 ± 8.48% ( P = 0.005). In isolated endometrial epithelial cells, leptin upregulated amounts of alpha v and beta 3 integrin, and promoted cell adhesion to such extracellular matrix proteins as fibronectin, laminin and type IV collagen, showing a dose- and time-dependent cell-adhesive capacity. Collectively, the information from the present study may partly account for leptin-induced mouse blatocyst implantation.