Environmental Factor – October 2024: Some endocrine disruptors may contribute to early puberty, study finds


Girls exposed to certain endocrine-disrupting chemicals (EDCs) may be more likely to start puberty early, according to a new study by NIEHS researchers.

“We conducted a comprehensive screen of 10,000 environmental compounds with extensive follow-up studies using human brain cells that control the reproductive axis, and our team identified several substances that may contribute to early puberty in girls,” said Natalie Shaw, M.D., who leads the Pediatric Neuroendocrinology Group at NIEHS.

Shaw leads the Pediatric Neuroendocrinology Group and holds a secondary appointment in the NIEHS Reproductive and Developmental Biology Laboratory. (Photo courtesy of Steve McCaw / NIEHS)

Those substances include a fragrance used in some detergents, perfumes, and personal care products.

“More research is needed to confirm our findings,” noted Shaw. “But the ability of these compounds to stimulate key receptors in the hypothalamus — the gonadotropin-releasing hormone receptor [GnRHR] and the kisspeptin receptor [KISS1R] — raises the possibility that exposure may prematurely activate the reproductive axis in children.”

The study, which was published in the journal Endocrinology, was funded by NIEHS and the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health.

Personal care products may contain EDCs

According to the research team, one of the EDCs identified — called musk ambrette — is potentially concerning because the fragrance can be found in personal care products, and some rat studies have suggested it can cross the blood-brain barrier.

Canadian and European regulations restrict musk ambrette use because of its potential toxicity, and the U.S. Food and Drug Administration removed the fragrance from its “generally recognized as safe” list. Yet, it is still available on the market in some personal care products.

“This study suggests that, out of an abundance of caution, it is important for parents to only use personal care products for their children that are federally regulated,” Shaw said.

Testing EDCs in new lab models

As part of the study, the research team screened a Tox21 10,000-compound library of licensed pharmaceuticals, environmental chemicals, and dietary supplements against a human cell line overexpressing GnRHR or KISS1R. They conducted follow-up analysis in human hypothalamic neurons and zebrafish as a model for identifying environmental substances that stimulate KISS1R and GnRHR.

“This study was a multidisciplinary team effort, and it showed that we can efficiently reduce the time and cost of assessing environmental chemicals for their potential effects on human health,” said co-author Menghang Xia, Ph.D., from NCATS.

Citation:
Yang S, Zhang L, Khan K, Travers J, Huang R, Jovanovic VM, Veeramachaneni R, Sakamuru S, Tristan CA, Davis EE, Klumpp-Thomas C, Witt KL, Simeonov A, Shaw ND, Xia M. 2024. Identification of environmental compounds that may trigger early female puberty by activating human GnRHR and KISS1R. Endocrinology 165(10):bqae103.

(This article is adapted from the Endocrine Society press release published September 10, 2024.)



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