Effects of Di-N-Butyl Phthalate on Ovulation, Fertilization, and Early Embryo Development in Female CD-1 Mice

Abstract

We have used a mouse model to evaluate the effects of short-term oral exposure to DBP at two environmentally relevant doses that are comparable to human exposure. To better characterize the effects of DBP on female fertility, we examined several fertility parameters including: ovulation, fertilization, early embryo development, fragmentation, early embryo viability, and COC transcriptomics. Our main findings show that at human relevant doses, DBP leads to increased embryonic fragmentation and altered mRNA expression of cumulus-oocyte-complexes, and that MBP accumulates in reproductive tissues following oral exposure to DBP. The present study reveals that DBP targets the ovary in adult mice and indicates that environmentally relevant oral exposures (10 and 100 µg/kg/day DBP) below the current oral reference dose of 300 µg/kg/day DBP set by the U.S. EPA compromises COC integrity by altering mRNA expression and increasing early embryo fragmentation, without adversely impacting ovulation or fertilization. Our findings on altered mRNA expression and increased fragmentation at environmentally relevant concentrations of DBP support the adverse reproductive outcomes seen in human studies which further suggest that DBP is a significant concern for human reproductive health [85,95,213]. Understanding how short-term environmentally relevant exposures to DBP and other phthalates affect reproductive health is critical information needed to better predict fertility and reproductive outcomes and better understand the risks associated with EDC exposure.