Up to 15% of women of reproductive age are infertile, with ovarian disorders as a leading cause. These disorders include primary ovarian insufficiency, polycystic ovary syndrome (PCOS), anovulation, and aneuploidy.
The underlying mechanisms of ovarian dysfunctions remain largely unknown, but studies have shown links to exposure to environmental endocrine disrupting chemicals (EDCs). In a recent webinar, Dr. Shuo Xiao introduced his lab research that focuses on integrating in vivo, in vitro, and in silico models to study the impacts of real-world EDC mixtures on female ovarian function, reproductive outcomes, and the molecular mechanisms involved.
Exposures linked to reproductive health
EDCs are chemicals that interfere with hormone-related functions of the endocrine and reproductive systems. They can alter hormonal signals that control and guide much of our growth and development, the way our organs function, and our ability to fight disease.
Common sources of EDCs include plastics and plasticizers, items treated with flame retardants, personal care products, food packaging, industrial chemicals, pesticides, wildfire smoke, and contaminated air and water.
Most prior research on the impact of EDCs on reproductive health focuses on exposure to a single chemical. However, in the real world people are exposed to complex EDC mixtures. Xiao’s lab uses a variety of methods to study EDC mixtures and the effects they have on women’s reproductive health. In his webinar, Xiao described some of the lab’s studies.
One study looked at how PFAS, including the chemical perfluorononanoic acid (PFNA), could adversely impact female ovary function. PFNA is an understudied PFAS that has been reported to reach similar or higher concentration levels of other, more well-studied PFAS, such as PFOA and PFOS. The study found evidence that PFNA can inhibit follicle development. Follicles exposed to the PFAS exhibited delayed follicle growth and less hormonal secretion. This could result in delaying ovulation and negatively impacting fertility.
Studying real-world mixtures
Another focus of study is cyanobacterial harmful algal blooms. Climate change together with eutrophication are making harmful algal blooms more common. These algal blooms produce many toxins, including one called microcystin-LR (MC-LR).
One of Xiao’s studies found that MC-LR can inhibit the enzyme protein phosphatase 1 (PP1) in the ovary. This enzyme plays an important role in follicle development. The study concluded that MC-LR may heighten the probability of irregular menstrual cycles and infertility related to ovulatory disorders.
To investigate the effects of real-world mixtures, Xiao’s lab analyzed samples from three rivers in New Jersey. They then recreated the mixtures found and gave it to mice in their drinking water. They also looked at the effects of the mixtures in vitro. In the mice, the mixtures interfered with estrous cycles. In humans, these impacts could lead to delayed or blocked ovulation. The study’s in vitro model showed similar effects to the in vivo model.
In looking for a possible molecular mechanism to explain these results, the researchers examined 25,000 genes. They found that EDC mixtures can change the expression of many genes, including several that play roles in hormone reception.
Ongoing & future research
Currently, there is very little understanding of how the various EDCs in a mixture interact to contribute to the overall effects of the mixture. This is an area of ongoing and future research that the lab is investigating.
Xiao closed his presentation by stressing that EDCs can be toxic to female reproductive health, and that EDC mixtures can be more harmful than the individual chemicals in the mixtures. More research using new study methods will be necessary before we have a full understanding of the dangers from these mixtures.
Xiao expressed hope that research such as this, along with risk assessment, would be used to guide policies to protect reproductive health.
Measures that individuals can take to reduce exposure include avoiding plastic (especially in the microwave) and avoiding contaminated lakes during algal bloom season. Xiao also stressed the importance of health education and communication.
For more, see our webinar co-hosted by the EDC Strategies Partnership and Young EDC Scientists Showcase: EDCs & Reproductive Health: Effects of chemical mixtures on ovarian function.
This organizational blog was produced by CHE's Science Writer, Matt Lilley.