Maternal Thyroid Disruption: A Probable Key Mechanism of Bisphenol S Induced Testis Development Alteration

Bisphenol S (BPS) has emerged as a common substitute for bisphenol A in various consumer products. However, growing evidence suggests that BPS is an endocrine disruptor with potential impacts on thyroid hormone (TH) regulation and testicular function. This study aims to assess the impact of thyroid disruption on testicular development following maternal exposure to BPS. Pregnant and lactating female Wistar rats were treated with either BPS or AT 1-850 (a thyroid hormone receptor antagonist). Testicular development was evaluated at gestational day 20 (GD20), postnatal day 21 (PND21), and postnatal day 35 (PND35) through histology, testosterone quantification, and assessments of SOX9 and CYP17A1 expression in Leydig and Sertoli cells at both protein and gene levels. BPS exposure significantly reduced body weight and relative testes weight in male offspring (PND21 and PND35), accompanied by a decrease in anogenital distance, serum testosterone levels and seminiferous tubule diameter, along with histopathological alterations of the tubules. Additionally, the development of the offspring's testes appears to be impaired following BPS exposure, as evidenced by the lower expression of two key factors, namely SOX9 and CYP17A1, at both protein and molecular levels. It is also important to note that the majority of the deleterious effects of BSP are also similarly observed following treatment with AT 1-850. Based on the consistent results between the BPS and AT 1-850-treated groups, we conclude that BPS disrupts testicular development in male offspring by blocking nuclear THRs following maternal exposure during both fetal and postnatal stages.