Exposure to phthalates: germline dysfunction and aneuploidy

Epidemiological studies continue to reveal the enduring impact of exposures to environmental chemicals on human physiology, including our reproductive health. Phthalates, a well characterized class of endocrine disrupting chemicals and commonly utilized plasticizers, are among one of the many toxicants ubiquitously present in our environment. Phthalate exposure has been linked to increases in the rate of human aneuploidy, a phenomenon that is detected in 0.3% of livebirths resulting in genetic disorders including trisomy 21, approximately 4% of stillbirths, and over 35% of miscarriages. Here we review recent epidemiological and experimental studies that have examined the role that phthalates play in germline dysfunction, including increases in apoptosis, oxidative stress, DNA damage, and impaired genomic integrity, resulting in aneuploidy. We will further discuss subject variability, as it relates to diet and polymorphisms, and the sexual dimorphic effects of phthalate exposure, as it relates to sex-specific targets. Lastly, we discuss some of the conserved effects of phthalate exposure across humans, mammalian models and nonmammalian model organisms, highlighting the importance of using model organisms to our advantage for chemical risk assessment and unveiling potential mechanisms that underlie phthalate-induced reproductive health issues across species.