title: 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.
authors.affiliation: DSAR-Bioimaging, Sanofi U.S. Inc., Bridgewater, NJ, USA.
authors.forename: James
authors.initials: J
authors.lastname: Cao
authors.affiliation: DSAR-Bioimaging, Sanofi U.S. Inc., Bridgewater, NJ, USA.
authors.forename: Xiaoyou
authors.initials: X
authors.lastname: Ying
authors.affiliation: DSAR-Preclinical Safety, Sanofi U.S. Inc., Bridgewater, NJ, USA. Electronic address: bruce.beyer@sanofi.com.
authors.forename: Bruce K
authors.initials: BK
authors.lastname: Beyer
authors.affiliation: DSAR-Preclinical Safety, Sanofi U.S. Inc., Bridgewater, NJ, USA.
authors.forename: Anthony M
authors.initials: AM
authors.lastname: DeLise
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D004622:Embryo, Mammalian / Q000378:metabolism*; D030762:Estrous Cycle; D005260:Female; D005333:Fetus / Q000378:metabolism*; D008156:Luciferases / Q000235:genetics; D049449:Luminescence; D008297:Male; D008822:Mice, Transgenic; D061848:Optical Imaging; D011247:Pregnancy
chemical_list: D052160:Benzothiazoles; C532924:D-luciferin; D008156:Luciferases
keywords: Bioluminescence; Embryo; Fetus; Fluorescence; Imaging; Intravaginal; Risk assessment; d-Luciferin