The use of optical imaging to assess the potential for embryo-fetal exposure to an exogenous material after intravaginal administration

Abstract

A β-actin-luc transgenic mouse model was used to evaluate whether embryo-fetal exposure could occur after intravaginal administration of a compound. A bioluminescent substrate, d-luciferin, was delivered intravaginally to mimic compound exposure to the female reproductive track and the embryo-fetus. Bioluminescence was observed throughout the reproductive tract during diestrus, but not during estrus, 2-5min after intravaginal d-luciferin administration to female β-actin-luc mice. Intravaginal administration of d-luciferin to wild-type females mated with male β-actin-luc mice indicated that the substrate reached the developing embryo-fetus, with bioluminescence corresponding to transgene expression in the embryo-fetus. d-Luciferin substrate rapidly reached the embryo-fetus regardless of the administration route (intravaginal, intraperitoneal, subcutaneous, or intravenous). Vaginal ligation appeared to block at least some direct exposure to the embryo-fetus, but did not prevent d-luciferin from eventually reaching the embryo-fetus. Additional work will be necessary to form the basis for a reliable assessment of the human risk for male-mediated teratogenicity.

Keywords: Bioluminescence; Embryo; Fetus; Fluorescence; Imaging; Intravaginal; Risk assessment; d-Luciferin.