ESPE Yearbook of Paediatric Endocrinology

Environ Pollut 361 (2024) 124890.PMID: 39236844

Brief Summary: This experimental study identified long-term changes in gene expression in the hypothalamic-pituitary (HP)-axis in murine models exposed to relevant doses of endocrine-disrupting chemicals (EDCs) during pregnancy and perinatal periods.

The authors used 3 common EDCs: bisphenol-S (BPS), 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) and 3,3′,5,5′-tetrabromobisphenol A (TBBPA), at relevant doses, to assess long term effect on the brain HP-axis gene expression, using mRNA-seq followed by qPCR. These EDCs caused specific long term gene expression changes in the CD-1 mouse HP-axis, exposed during pregnancy and lactation. Exposure timing focused on pregnancy from day 8 through weaning, which captures critical developmental windows for neuroendocrine brain regions. The authors use multi-tiered molecular analysis, RNA seq and RT qPCR for pituitaries and hypothalamus that allows both broad screening and focused gene validation. The authors use (0.2 mg/ml) concentration of EDCs which approximates environmentally relevant exposures, enhancing translational significance. All 3 chemicals down regulated pituitary genes tied to endocrine function (Gh, LHb, CRH), with BPS and BDE 47 showing strong overlap in affected pathways. Across the board, there was reduced expression in immune-related genes and GPCR-mediated signalling cascades, indicating altered hormone responsiveness and immune surveillance at the pituitary level. In the hypothalamus the authors report down regulation of important hypothalamic function genes such as Esr1, Crh, Ghrh, among others.

Future studies are needed to functionally characterise these transcriptional changes and their physiological impact in isolation or in combination. The authors studied only males; future studies should use a non-sex biased approach to understand the effect of these EDCs in females. The study offers compelling evidence that low level developmental exposure to ubiquitous EDCs can reprogram central endocrine regulators. These findings set a new paradigm in understanding how environmental contaminants shape lifelong health outcomes.