The UV filter benzophenone 3 alters blastocysts implantation and the early embryonic development

ABUD J.E.; PAGOTTO, ROMINA; ZENCLUSSEN, MARÍA LAURA; GALLEANI, VALENTINA; BOLLATI-FOGOLÍN, MARIELA; RODRIGUEZ, H.A.

Mar del Plata

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021 SAIC - SAI - AAFE - NANOMED-ar; 2021

SAIC - SAI - AAFE - NANOMED-ar

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 evidenced the ability of BP3 to act like an endocrine disrupting chemical. The present study focuses on the effect of BP3 on the migration capacity of human trophoblast cells (Swan 71 cell line) and the potential involvement of the androgen receptor (AR) pathway. We analyzed three different BP3 concentrations: a) BP3-2: the predicted no-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, AR, matrix metalloproteinase 2 (MMP2), inhibitor of MMP-2 (TIMP2) and laminin a4 (LAMA4). The three doses of BP3 reduced the area of wound closure after 24 h of exposure, evidencing reduced migration of Swan 71 cells when compared to the vehicle. Interestingly, BP3 induced an augmented expression of AR mRNA levels in all concentrations assayed, and of TIMP2 and LAMA4 only in BP3-2. MMP-2 did not show significant changes. 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 24h, clearly indicating that BP3 acts through a AR-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 AR 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 AR-dependent pathway.