Benzo[a]pyrene Disrupts Gene Expression Vital for Human GnRH Neuron Development

Transcriptomic profiling of human fetal gonadotropin-releasing hormone neuroblasts indicates that exposure to benzo[a]pyrene directly compromises cell development by altering the expression of genes required for migration and adhesion. The RNA sequencing investigation revealed 585 significantly differentially expressed genes in treated cells, demonstrating that the environmental pollutant interferes with molecular pathways essential to neuroendocrine maturation.

Gonadotropin-releasing hormone neurons control reproductive function and depend on a tightly regulated migratory process during embryonic development. Benzo[a]pyrene, a widespread polycyclic aromatic hydrocarbon, has established associations with adverse reproductive outcomes, but its effects have historically been described primarily at the gonadal level rather than in neuroendocrine regulation. In earlier work, researchers established that exposing human fetal GnRH neuroblasts, designated as FNCB4 cells, to 10 micromolar benzo[a]pyrene for 24 hours impaired their migration and maturation.

To clarify the molecular mechanisms driving this impairment, the investigators conducted RNA sequencing on FNCB4 cells following benzo[a]pyrene treatment. The resulting transcriptomic dataset highlighted 585 differentially expressed genes meeting a false discovery rate threshold of less than 0.05. Functional and pathway enrichment analyses revealed that the affected genes were predominantly involved in cell adhesion, cell migration, and extracellular matrix organization.

The altered transcripts included critical genes governing GnRH neuron development and guided movement. Exposure changed the expression of cell adhesion molecules such as SDC2, SDC4, and ITGB5, as well as guidance receptors and ligands including FGFR1, SEMA5A, ROBO2, EFNA5, and EPHA5. In addition, the treatment modified the expression of JAG1, a ligand belonging to the Notch signaling pathway.

Network analysis further identified functional connections between multiple differentially expressed genes and RhoA, a recognized central regulator of cytoskeletal dynamics. In parallel immunofluorescence experiments, benzo[a]pyrene exposure inhibited RhoA membrane translocation, pointing to reduced RhoA activation and disrupted cytoskeletal remodeling essential for cell motility. While the researchers cautioned that the findings were obtained within a single in vitro neuroblast model, the results provide a molecular basis for benzo[a]pyrene reproductive toxicity operating at the central nervous system level.

Subject of Research: Effects of benzo[a]pyrene on human GnRH neuron differentiation and gene expression

Article Title: Transcriptomic profiling supports deleterious effects of benzo(a)pyrene on human gonadotropin-releasing hormone neuron differentiation

Article References: Guarnieri, G., Lazzerini, L., Mattei, G., Mencarelli, F., Becatti, M., Paternostro, F., Musil, Z., Zapletal, J., Zach, P., Magi, A., & Morelli, A. (2026). Transcriptomic profiling supports deleterious effects of benzo(a)pyrene on human gonadotropin-releasing hormone neuron differentiation. Cell Biology and Toxicology. https://doi.org/10.1007/s10565-026-10290-0

Image Credits: AI Generated

DOI: 10.1007/s10565-026-10290-0

Keywords: benzo[a]pyrene, GnRH neurons, neurodevelopment, transcriptomics, cell migration, FNCB4 cells, RhoA, reproductive toxicology, Transcriptomic, profiling, supports, deleterious