Exposure to Antimicrobials During Development May Cause Irreversible Outcomes

“Our results are significant because of the potential risk of exposure to TCC through contaminated water sources and in the living environment, and the potential adverse effects resulting from this exposure during development,” said LLNL biologist Heather Enright, the lead author of the paper. “Early life exposure to TCC has the potential to cause irreversible outcomes due to the fragile nature of organ systems and protective mechanisms in developing offspring.”

The team studied mice during gestation and lactation to see if, in fact, exposure to TCC would transfer from mother to offspring. Researchers administered TCC laced with carbon-14 to trace how the contaminant distributed in organ systems of female mice and exposed offspring.

Using accelerator mass spectrometry (AMS), Enright and her colleagues quantified TCC concentrations in offspring and their mothers after exposure. AMS fills a special niche in the biomedical field because it can measure very low concentrations of compounds with extreme accuracy and track bio-distribution and excretion over long periods of time.

“We demonstrated that TCC does effectively transfer from mother to offspring, both trans-placentally and via lactation,” Enright said. “Exposure to TCC during development may pose a serious health risk to the developing embryo and fetus, as they are more sensitive to alterations in hormone levels, which may result in changes that often are irreversible.”

TCC-related compounds were detected in the tissues of offspring with significantly higher concentrations in the brain, heart and fat. In addition to the transfer from mother to offspring, exposed offspring were heavier in weight than unexposed mice — demonstrating an 11 percent and 8.5 percent increase in body weight for females and males, respectively.

Quantitative real-time polymerase chain reaction (qPCR) was used in the study to examine changes in gene expression in liver and adipose tissue in the exposed offspring. The results suggested alterations in genes involved in lipid metabolism in exposed female offspring were consistent with the observed increase in fat weights and hepatic triglycerides.

Other Livermore researchers include Miranda Falso (now at Slippery Rock University), Michael Malfatti, Victoria Lao, Edward Kuhn, Nicholas Hum, Yilan Shi (now at Bio-rad), Ana Sales, Kurt Haack, Kristen Kulp, Bruce Buchholz, Gabriela Loots, Graham Bench and Ken Turteltaub. The work was funded by LLNL’s Laboratory Research and Development Program and the National Institutes of Health.

Contacts and sources
Lawrence Livermore National Laboratory