"I am still amazed by the biology of this 1mm long nematode," says Dr Samantha Hughes, Assistant Professor in the Environmental Health and Toxicology department at the Vrije Universiteit Amsterdam, a MERLON partner, "Even after all this time, I find it fascinating to watch their eggs being fertilised and the first few cell divisions."
Samantha has worked with tiny Caenorhabditis elegans roundworms for over 20 years – using them to understand how environmental chemicals, like pesticides and endocrine disrupting chemicals (EDCs) such as PFAS, affect human health.
These worms act as a window into our health as they share surprising similarities with humans. They mirror many fundamental biological processes like growth, development, and metabolism - and most importantly for the MERLON project, reproduction.
They also have other unique features making them ideal for reproductive health research. As self-fertilising hermaphrodites, a single worm can produce up to 300 genetically identical offspring. Their three-day life cycle allows researchers to study multiple generations in weeks rather than years, and they can be examined at all developmental stages.
"Working with C. elegans enables fast experimental analysis of biological processes that can be translatable to higher organisms, like rodents and humans," says Samantha making them ideal for studying how environmental toxins affect development and reproductive health over several generations.
Their regulatory classification offers another advantage. "They are, somewhat counterintuitively, not considered 'animals' as per certain legal guidelines, which means we do not require special approval to work with them," Samantha explains.
Samantha acknowledges that research using C. elegans has its limitations. They lack a complex immune and cardiovascular system, and absorb and process chemicals differently, so findings need to be confirmed by further research to be applied to human health.
When it comes to reproductive health research, however, worms and humans have a crucial process in common – they both fertilise their eggs and development begins internally. This allows researchers to expose worms to EDCs very early in their development to see how this affects their reproductive systems, fertility, and overall development.
Understanding how environmental toxins affect health brings its own set of challenges, but that's also what keeps Samantha interested in her research. "I think I get the most excitement from being a scientific detective," she says, "when there is an impact of a chemical on brood size, we try and work out how this happens – is it a change in a gene being on or off, are there less sperm, does the mum not prepare her eggs properly?"
Through their work, Samantha and her team contribute to reducing and refining animal models in toxicity testing. Despite the potential for eco-toxicological risk assessment, C. elegans use in this area remains limited. "MERLON will be an important step in validating C. elegans as a new approach methodology, an important step for implementation into human health risk assessment and decision making," she says.
The impact of her research goes beyond the lab. Increasing concerns about chemicals and their impact on fertility and reproductive health means that this has significant implications for public health policy.
"We know that exposure to chemicals, especially EDCs, results in an interaction with reproductive processes," she says, "Tackling this issue is really important to protect human reproductive health for current and future generations."
