The UV filter benzophenone 3 (BP3) alters the migration of the extravillous trophoblast cell line Swan 71 via androgen receptor pathway

ABUD, JULIÁN; PAGOTTO, ROMINA; ZENCLUSSEN, MARÍA LAURA; GALLIANI, VALENTINA; BOLLATI-FOGOLÍN, MARIELA; RODRÍGUEZ HORACIO ADOLFO

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXIX Reunión Anual de la Soc. Argentina de Inmunología (SAI); 2021

Sociedad Argentina de Investigación Clínica

BP3 is one of the most commonly substances used in sunscreens and personal care products due to its UV blocking efficacy. Several in vitro and in vivo studies have evidenced the ability of BP3 to act like an endocrine disrupting chemical. The present study focuses on the effect of BP3 on the migration ability of human trophoblast cells (Swan 71) and the potential involvement of the androgens receptor (RA) pathway. We analyzed three different BP3 concentrations: a) BP3-2: the predicted non-effect concentration (2 μg/L), b) BP3-20: the concentration detected in the amniotic fluid (20 μg/L) in our previous studies and c) BP3-200: the plasma concentrations reported in humans (200 μg/L). We examined cell migration activity by scratch-wound healing assay, as well as mRNA relative expression levels of molecules of interest such as Survivin, E-cadh, DNMT1, MMP2, TIMP2, RA and LAMA4 . The three doses of BP3 reduced the area of wound closure after 24 h presented, evidencing reduced migration of Swan 71 cells when compared to the vehicle. Interestingly, BP3 induced an augmented expression of RA mRNA levels in all concentrations assayed. In order to confirm whether BP3 acts via an AR-dependent pathway, we then analyzed BP3 effects with and without an AR inhibitor (Flutamide, 1 µM). When the cells were treated with BP3 in the presence of flutamide, the area of wound closure did not change after 24 h, clearly indicating that BP3 acts through a RA-dependent pathway. This was confirmed by the AR mRNA expression restoration in cells exposed to BP3 + flutamide. In conclusion, exposure to relevant doses of BP3 is enough to perturb the migration capability and the expression of RA mRNA levels of the trophoblast cell line Swan 71. These effects were reversed in the presence of an AR inhibitor indicating that BP3 could act via RA-dependent pathway