CONICET | Buscador de Institutos y Recursos Humanos

The aim of our study is to analyze the effect of the UV-filter benzophenone 3 (BP3) on early gestational processes by a complementary in vitro and in vivo approach. Using an in vitro assay of blastocyst implantation, we analyzed the effect of three different BP3 concentrations: a) BP3-2: the predicted non-effect concentration (PNEC: 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). Blastocysts from 3.5 days pregnant mice (C57BL/6J) were transferred to a monolayer of autologous uterine epithelial cells (UECs) and cultured in the presence of vehicle (0.01 % DMSO) or BP3 for 6 days. Blastocyst expansion, hatching and implantation in the monolayer as well as implantation area were analyzed microscopically and recorded every 12 h. To verify the in vivo relevance of the in vitro results, pregnant C57BL/6J mice were exposed via dermal route to BP3-50 (50-mg BP3 kg.day) or olive oil (vehicle) from gestation day (gd) 0 to gd10. The mice were sacrificed at gd10 and the size of the whole implantation sites (WIS) was measured.In vitro exposure to BP3-2 and BP3-200 altered the blastocysts expansion. Moreover, the hatching and the implantation time were delayed and the implantation areas were significantly smaller than those from the control with all BP3 concentrations assayed. In vivo study reaffirms the in vitro results, since we found that BP3-50-exposed WIS was smaller than those exposed to the vehicle. Previously, we showed that in vivo dermal BP3-50 produced an intrauterine growth restriction (IUGR) phenotype and lower offspring weight of first progeny. Here, we could demonstrate that BP3 disrupt blastocyst implantation and early embryo development. Our results suggest that an underlying mechanism by which BP3 affects pregnancy are linked to disruption of the implantation stage, leading consequently to a reduction in embryo size.