UC San Francisco scientists develop new method using yeast to find chemicals that cause infertility

Using a new method to test chemical toxicity, UC San Francisco (UCSF) scientists have revealed a growing list of chemicals that could cause reproductive harm, including infertility.

“With infertility a growing problem around the globe, it is important to find better strategies to discover the root causes,” said Tracey J. Woodruff, PhD, director of the UCSF Program on Reproductive Health and the Environment and the UCSF EaRTH Center. “Our study found more chemicals toxic to the reproductive system than we previously knew.”

Published June 19 in the journal Reproductive Toxicology, the scientists write, “Many of the ~40,000 chemicals that are actively manufactured, imported, or used in household or commercial products have not been evaluated for their potential toxicities towards human health. Reliable information about reproductive toxicology is particularly scarce, even for those chemicals commonly detected in maternal and umbilical cord sera.”

The scientists evaluated 199 chemicals including bisphenols, phthalates, pesticides, PFAS (“forever chemicals”), and quaternary ammonium compounds and found 57 strongly negatively impacted the reproductive system. They found many new BPA substitutes, which are used in plastic water bottles and other plastic products, are actually more toxic than the original bisphenol A and that when certain BPA and BPA-type chemicals were combined, reproductive outcomes worsened.

“One of the reasons it is so challenging to determine reproductive toxicity is that the adverse effects that take place in female fetuses in utero are not observed until adulthood,” said senior author Jennifer Fung, PhD, professor of Obstetrics, Gynecology and Reproductive Science and director of the EaRTH Center’s Bioassay Core. “Relating chemical exposure in an individual to fertility reduction in their children, or birth defects in their grandchildren, is even more challenging.”

With the huge number of untested chemicals currently in use, some method is needed to figure out which ones could be hazardous to reproduction.  Testing them in animals like mice is prohibitively expensive, because finding an effect on reproduction requires the mice to be raised for three generations.  To evaluate large numbers of chemicals for reproductive toxicity, the scientists applied chemicals to S. cerevisiae, a yeast that is a common laboratory organism that is used to study gametogenesis, a process essential to make sperm and eggs for successful reproduction. Human and yeast genes are extraordinarily similar, with about 60% of yeast genes having a human equivalent and 87% of yeast proteins are present in human biological systems.

In addition to finding that many BPA substitutes are more toxic than the original chemicals they found most highly toxic to the reproductive system included cadmium chloride (used in dyeing and printing textiles), bisphenols AF, AP, BPZ, PH and E (used in the production of plastics and resins) and several quaternary ammonium compounds including ODDAC and 1-(Benzyl)quinolinium chloride (used in disinfectants and sanitizers).

“Many of these chemicals are interfering with the ability of eggs to fertilize,” said lead author Ravinder Kumar, PhD in the Department of Obstetrics, Gynecology, and Reproductive Sciences at UCSF.

Woodruff also said their study should raise red flags for EPA. “We keep seeing quaternary ammonium compounds come up as toxic in the research and EPA is not looking at these chemicals, which are widely used,” she said. Quaternary ammonium compounds are found in heavy duty cleaning products and are highly toxic.

While more research is needed to determine how to translate the yeast findings for predicting effects in humans, they are a clear indication that we should act to prevent potentially harmful exposures.

The study was funded by the National Institute of Environmental Health Sciences (NIEHS), UCSF EaRTH Center (P30-ES030284) and UCSF National Center of Excellence in Women’s Health.

Paper:
Rapid identification of reproductive toxicants among environmental chemicals using an in vivo 2 evaluation of gametogenesis in budding yeast Saccharomyces cerevisiae

Authors:
Ravinder Kumar, Ashwini Oke, Beth Rockmill, Matthew de Cruz, Rafael Verduzco, Anura Shodhan, Xavier Woodruff-Madeira, Dimitri P. Abrahamsson, Julia Varshavsky, Juleen Lam, Joshua F. Robinson, Patrick Allard, Tracey J. Woodruff, and Jennifer C. Fung.