Parallel assessment of the effects of early life exposure to bisphenol S and inhibition of nuclear receptor of thyroid hormones on bone development

Environmental exposure to endocrine-disrupting chemicals has become a growing public health concern, particularly during critical periods of development. Bisphenol S (BPS), a widely used substitute for bisphenol A (BPA), has attracted increasing attention due to its potential endocrine-disrupting properties, especially its effects on thyroid function. Given reported interactions of BPS with thyroid hormone nuclear receptors (THNRs) and the essential role of thyroid hormones in fetal growth and skeletal development, we hypothesized that maternal exposure to BPS may impair pre- and postnatal bone development through disruption of thyroid homeostasis. To test this hypothesis, pregnant and lactating Wistar rats were exposed daily to BPS (0.2 mg/kg) or to the thyroid hormone receptor antagonist AT1–850 (10 nmol/rat), used here as a mechanistic reference compound. In 20-day-old male fetuses, both treatments induced significant abnormalities in the axial skeleton. By postnatal day 21, male offspring exhibited marked histological alterations in bone structure, increased oxidative stress, and a significant downregulation of key osteogenic markers, including RUNX2, alkaline phosphatase (ALP), collagen type I alpha 1 (Col1α1), and osteocalcin (OCN). Notably, similar patterns were observed following exposure to BPS and AT1–850. These findings suggest that BPS exposure during critical developmental windows may impair bone development, potentially through disruption of maternal thyroid hormone signaling pathways.