PROTECT research findings suggest toxicant exposure may inhibit tissue resistance to microbial infections during pregnancy

proj 2PROTECT investigators are conducting innovative studies using in vitro models of human gestational tissues to better understand relationships between toxicant exposures and preterm birth.

Microbial infection of the maternal reproductive tract is one of the most common known causes of preterm birth and pregnancy complications, yet the ability of toxicants to modify susceptibility to microbial infection is poorly understood.

Boldenow 2015

Fig 1. DCVC inhibition of GBS-stimulated cytokine release from human extraplacental membranes. Adapted from: Boldenow et al., 2015.

Using explant cultures of human extraplacental membranes (the tissue that forms the gestational compartment), Project 2 investigators found that exposure to S-(1,2-dichlorovinyl)-L-cysteine (DCVC), a bioactive metabolite of trichloroethylene (TCE), inhibits pathogen-stimulated cytokine responses that are important for tissue defense against infection.

Figure 1 shows that live Group B Streptococcus, added to the maternal side of the extraplacental membranes in transwell cultures, strongly stimulates innate immune defense responses with release of the cytokines TNF-α and IL-1β in the absence of DCVC but not in the presence of DCVC (Figs. 1a and 1b, respectively; Boldenow et al., 2015). This study shows toxicant-microbial interactions with potential implications for pregnancy.