Common plastic chemical could threaten fertility of humans worldwide
By Study Finds
Could a common plastic chemical be hindering human fertility on a global level? Harvard Medical School researchers have uncovered new evidence about a chemical that’s nearly impossible to avoid: benzyl butyl phthalate (BBP), found in everything from vinyl flooring to children’s toys, may be affecting reproductive cells at concentrations commonly detected in human blood samples.
BBP belongs to a family of chemicals called phthalates that manufacturers use as plasticizers – additives that increase the flexibility and durability of plastic products. Beyond vinyl flooring and toys, BBP appears in carpet backing, food packaging, and personal care products. The compound has been identified as an endocrine-disrupting chemical, meaning it can interfere with hormone systems in the body.
To study BBP’s effects on reproduction, the research team used Caenorhabditis elegans (C. elegans), microscopic worms that share significant genetic similarities with humans. Using these transparent worms allows scientists to directly observe changes in reproductive organs while working with an organism that has similar reproductive processes to humans.
Using a specialized strain of C. elegans modified to be more permeable to chemicals, the researchers tested various concentrations of BBP: 1, 10, 100, and 500 micromoles. Their findings revealed an unexpected pattern – exposure to 10 micromoles of BBP caused the most significant damage, resulting in a 1.71-fold increase in X-chromosome segregation errors. This phenomenon, where lower doses can cause more severe effects than higher doses, is known as a “non-monotonic dose response.”
When the researchers examined BBP’s effects more closely, they found multiple signs of cellular damage. The chemical triggered increased cell death in reproductive organs, disrupted normal chromosome organization, and activated DNA damage response systems. They also observed elevated levels of oxidative stress throughout the reproductive organs of exposed worms.
The study, published in PLOS Genetics, revealed that these worms process BBP similarly to humans, breaking it down into two primary metabolites: monobutyl phthalate (MBP) and monobenzyl phthalate (MBzP). Critically, the concentrations of BBP and its metabolites found in worms exposed to 10 micromoles matched levels previously reported in human biological samples. For context, similar concentrations have been detected in human cord blood (0.089 micrograms per milliliter), maternal urine (up to 0.336 micrograms per milliliter for MBzP), and amniotic fluid (up to 0.263 micrograms per milliliter for MBP).
The researchers also discovered that BBP exposure altered the expression of 344 genes in the worms. These affected genes play crucial roles in how cells handle toxic substances, maintain their structural organization, regulate the reproductive cycle, and manage oxidative stress. This widespread change in gene activity suggests BBP’s effects may be more complex than previously understood.
Further analysis revealed that exposed worms showed problems with chromosome organization during the formation of reproductive cells. The researchers observed increased DNA double-strand breaks throughout the reproductive organs and defects in chromosome structure in developing eggs. These effects were accompanied by the activation of a DNA damage checkpoint system controlled by a protein called p53, known for its role in protecting cells from damage.
The implications of these findings extend beyond the laboratory worms. While the study cannot directly predict BBP’s effects in humans, the similar concentrations where effects were observed and the shared biological processes between worms and humans suggest potential concerns for human reproductive health. The fact that these effects occur at concentrations already found in human biological samples makes these findings particularly relevant for public health considerations.
The research adds to growing evidence that common plastic additives may affect reproductive health in previously unexpected ways, particularly at low concentrations. This study’s findings about non-monotonic responses also raise important questions about how we evaluate chemical safety, suggesting that even low-level exposures to BBP warrant careful consideration.
Paper Summary
Methodology
The researchers used a specialized strain of C. elegans worms that had been modified to be more permeable to chemicals and to show visible signs when chromosome segregation errors occurred. They exposed these worms to different concentrations of BBP for 24 hours and then used various techniques to examine the effects. These included fluorescence microscopy to visualize DNA damage, mass spectrometry to measure BBP levels in the worms, and RNA sequencing to analyze changes in gene expression. They also used special reporter worms that could show when oxidative stress was occurring in their reproductive organs.
Key Results
The study found that exposure to 10 micromoles of BBP caused the strongest effects, including a 1.71-fold increase in chromosome segregation errors, increased cell death in reproductive organs, and widespread DNA damage. The researchers detected BBP and its metabolites in the worms at levels similar to those found in human biological samples. They also identified 344 genes that showed significant changes in expression after BBP exposure.
Study Limitations
While C. elegans is a useful model organism, it’s still a worm and not a human, so the results may not translate directly to human health effects. The study also looked at relatively short-term exposure (24 hours) and couldn’t assess long-term effects or impacts across generations. Additionally, humans are typically exposed to multiple phthalates and other chemicals simultaneously, while this study only looked at BBP in isolation.
Discussion & Takeaways
The study suggests that BBP exposure, even at levels similar to human exposure, can damage reproductive cells through multiple mechanisms, including DNA damage, oxidative stress, and altered gene expression. The non-monotonic dose-response observed is particularly concerning as it suggests that even low-level exposure might be harmful. The research adds to growing evidence that common plastic additives might be affecting reproductive health more significantly than previously thought.
Funding & Disclosures
The research was supported by the McKenzie Family Trust, a Ford Foundation Fellowship Scholar Award, and the National Institutes of Health’s National Institute of Environmental Health Sciences. The authors declared no competing interests.
Source: Study Finds
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