Tox21 Team Finds Environmental Chemicals That Could Trigger Early Puberty in Girls
Dec. 9, 2024
Doctor and hologram of the female reproductive system. (Shutterstock)
What’s behind the rising trend toward earlier puberty in girls? NCATS researchers in the Toxicology in the 21st Century (Tox21) program teamed with their partners at the National Institute of Environmental Health Sciences and Northwestern University to test thousands of environmental chemicals to try to answer that question.
Like searching through a chemical haystack for a few needles, the research team tested roughly 10,000 compounds to find ones that might start puberty early. The Tox21 library includes pharmaceutical and environmental compounds. The scientists focused on how those compounds affect nerve cells in the hypothalamus. The hypothalamus is a part of the brain that controls the reproductive system. Stimulating those nerve cells leads to the production of the sex hormones estrogen and testosterone.
The Tox21 team’s study appeared in the journal Endocrinology.
The researchers used quantitative high-throughput screening (qHTS) to search the library quickly. Cell-based tests called assays helped them see which compounds either turned on or turned off hypothalamus nerve cells’ receptors of two molecules: kisspeptin and gonadotropin-releasing hormone (GnRH). Those nerve cells’ kisspeptin and GnRH receptors play a key role in the control of pubertal timing.
The team’s search led them to a handful of compounds that activate kisspeptin or GnRH receptors, including one called musk ambrette. Musk ambrette is a fragrant chemical often used in perfume, lotion, soap and detergent.
In several tests, the research team found that musk ambrette activated kisspeptin receptors in reproductive nerve cells. Musk ambrette also increased expression of the gene that encodes for GnRH in mouse and human cell models. In another test, musk ambrette boosted GnRH levels in the reproductive nerve cells of developing zebrafish larvae.
“Combining qHTS methods with comprehensive assays using human hypothalamic cells and zebrafish models can help rapidly identify environmental chemicals that may have toxic effects on the reproductive system,” said Menghang Xia, Ph.D., an author of the study and a systems toxicology leader in NCATS’ Division of Preclinical Innovation.
Given the study findings, the research team noted that musk ambrette or related synthetics in the environment may be contributing to the trend of early puberty in girls and deserve a closer look.