EFFECT OF ENDOCRINE DISRUPTORS ON HUMAN ENDOMETRIAL STROMAL CELLS AND THEIR INTERACTION WITH TROPHOBLAST

Decidualization is crucial for embryo development and implantation, placenta formation and fetal growth. This process is characterized by morphological and biological changes in endometrial stromal cells that play a key role on fetal trophoblast migration and invasion. Successful placentation depends on the interaction between endometrial stromal cells and extravillous trophoblast cells. The trophoblast spheroids, a 3D culture model, is reported to appropriately mimic the in vivo situation, and reflect the cell to cell interaction. The Bisphenol A (BPA) and para-nonylphenol (p-NP) are endocrine disrupting chemicals (EDCs), present in the polycarbonate plastics used in many products such as food packaging, bottles and beverage cans and as an intermediate in the production of phenolic resins. Studies demonstrated that maternal exposure to EDCs, at environmentally relevant concentrations, are associated to aberrant early embryo development and uterine receptivity due to their estrogenic activity. Nowadays it is known that environmental contaminants can change stromal cell decidualization and trophoblast migration. In the present study, we developed a simple 3D culture model using transformed human endometrial stromal cells (tHESCs) and immortalized first trimester human extravillous trophoblast cells (HTR-8/SVneo). The aim of this work was to evaluate the effect of BPA and p-NP on endometrial stromal cells during decidualization and their interaction with trophoblast spheroids. The data showed that pre-exposition to p-NP of endometrial stromal cells impaired decidualization interfering on the cross-talk with trophoblast and altering lysosomes biogenesis and consequently leading to an impairment in trophoblast migration.