Uterine fibroid growth increases with cadmium exposure, but not because cadmium acts like estrogen

Breathing or eating even small amounts of the toxic metal cadmium—a widespread contaminant of cigarettes and seafood—may increase a woman’s risk for developing uterine fibroids, but not in the way scientists previously thought. By the age of 50, at least seven out of ten American women will have developed these benign tumors that can cause infertility and miscarriage. Scientists have long suspected that cadmium encourages fibroid growth by mimicking the natural hormone estrogen. However, new research published this month in Environmental Health Perspectives indicates that cadmium may instead encourage fibroid growth through a molecular pathway involved in a third of all tumors. The North Carolina researchers suggest that treatments targeting this pathway may block cadmium’s dangerous effects, and help limit the growth and damage of uterine fibroids in women.

To figure out how cadmium encourages fibroid growth, the researchers added it to different types of uterus-like cells grown in Petri dishes. When they grew the cells with low concentrations of cadmium—concentrations similar to the cadmium blood levels of more than 70% of Americans—they found that the metal greatly increased the number of cells, similar to how estrogen increases the number of uterus cells. But the similarity stopped there: while estrogen increased cell growth by interacting with estrogen receptors—molecules on a cell’s surface which relay signals to its nucleus, thereby affecting which genes turn on and off—the cadmium did not interact with the estrogen receptors.

So how was cadmium increasing the uterus cells’ growth? The researchers figured out the answer when they looked at other molecules involved in cell signaling—specifically, the MAPK pathway, a series of signal molecules involved in both healthy cell growth and cancerous cell growth. When they exposed the uterus cells simultaneously to cadmium and to chemicals that interfere with the MAPK pathway, they found that cadmium couldn’t increase cell growth. While cadmium didn’t increase cell growth by interacting with estrogen receptors, the researchers suggested that it may act together with estrogen naturally present in a woman’s body (or estrogen-like molecules such as bisphenol A) to increase fibroid growth more than cadmium or estrogen alone could.

Gao X, Yu L, Moore AB, Kissling GE, Waalkes MP, & Dixon D (2015). Cadmium and Proliferation in Human Uterine Leiomyoma Cells: Evidence of a Role for EGFR/MAPK Pathways but Not Classical Estrogen Receptor Pathways. Environmental health perspectives, 123 (4), 331-6 PMID: 25343777