Citation:

Conley, J., C. Lambright, N. Evans, V. Wilson, AND L. Gray. Antiandrogen mixology: Cumulative effects of environmental chemicals on male rat reproductive tract development. Society of Toxicologic Pathology Annual Symposium, Raleigh, NC, June 22 - 27, 2019.

Impact/Purpose:

This abstract is for an invited platform presentation at the Society of Toxicologic Pathology Annual Symposium. The presentation is intended to review our historical and recent research regarding the cumulative effects of in utero exposure to mixtures of compounds that interfere with the fetal androgen signaling pathway. Further the talk will cover our use of adverse outcome pathway (AOP) networks as a conceptual model for the design and evaluation of mixtures studies.

Description:

Male reproductive impairments, such as hypospadias, cryptorchidism and reduced sperm counts, are relatively common and have reportedly been increasing in prevalence over the last several decades. These effects can be induced in laboratory animals by a wide range of environmental chemicals via diverse molecular mechanisms. For example, in utero exposure to androgen receptor (AR) antagonists and some phthalates disrupt male reproductive tract development; however, phthalates decrease fetal testicular testosterone production, whereas AR antagonists directly interfere with receptor signaling but do not affect fetal testosterone production. We have incorporated these diverse mechanisms into an Adverse Outcome Pathway (AOP) network that serves as a conceptual model for the design and evaluation of complex mixtures studies of chemicals that target different molecular mechanisms. Results of multiple studies indicate that, despite acting through disparate molecular mechanisms, chemicals impacting male reproductive development act cumulatively to produce adverse effects similar to those observed in human populations. Moving forward, AOP networks provide a mechanistically-based framework for grouping chemicals, addressing mixture hazards, and in conducting cumulative risk assessments. Abstract does not necessarily reflect USEPA policy.

Record Details: