Endocrine Disruptors at the Fetomaternal Interface: Insight From PBDE Studies and the Utility of Novel Approach Methods

Endocrine mediators are essential for pregnancy maintenance, and their functional withdrawal is associated with normal term and preterm birth (PTB). Therefore, the disruption to endocrine functions or agents that can disrupt endocrine functions are naturally suspected as contributors to PTB. One of the well-studied endocrine-disrupting compounds is polybrominated diphenyl ether(s) (PBDE). PBDE is a flame-retardant compound that is contained in several products and is a ubiquitous environmental contaminant. PBDE exists in several different congeners, many harmless compounds, but a few PBDE congeners are linked as endocrine disruptors contributing to adverse pregnancy outcomes like PTB. However, data ambiguity suggests that current platforms are insufficient to conclude PBDE's mechanisms of action as an endocrine disruptor at the fetomaternal interface (FMI) (placenta/fetal membranes). The development of microfluidic-based new approach methods (NAMs) is being introduced to study PBDE and other environmental pollutants. Organs-on-a-chip (OOCs) are an emerging class of NAMs that can replicate human organ-level functions in vitro. OOCs are microfluidic systems comprising multiple cell types from an organ that mimics the environment of a physiological organ. These devices are interconnected through microchannels to maintain intercellular interactions. OOC-based testing and development have accelerated globally as regulatory agencies now emphasize the need for reliable, humanized alternatives to traditional animal models. Multiple reproduction-associated OOCs are being developed, and their utility has been tested in assessing mechanisms of action and toxicological parameters of environmental pollutants. This review provides an overview of FMI OOCs and uses PBDE as an example to demonstrate how OOCs can study endocrine-disrupting compounds.