Lifelong impact of BPA: Steroidogenic reprogramming in aged gerbil adrenal glands following developmental exposure

Abstract

Endocrine-disrupting chemicals, particularly bisphenol A (BPA), are ubiquitous environmental contaminants that can profoundly affect hormonal systems and human health. The effects are variable and are contingent upon the developmental stage at which exposure occurs. This study aimed to investigate the effects of intrauterine and lactational BPA exposure on the adrenal glands of aged Mongolian gerbils (Meriones unguiculatus). In a controlled experimental set-up, pregnant gerbils were assigned to control or BPA-exposed groups, with the BPA group receiving a high dose during critical periods of development to assess the subsequent effects on adrenal gland function in their offspring at senile age. Biometric and hormonal assessments (estradiol, cortisol and testosterone) were conducted. Immunohistochemical and immunofluorescence analysis assessed steroidogenic activity related to testosterone production (StAR, CYP17, 3βHSD, 17βHSD, testosterone, 5α-reductase and CYP19), expression of hormone receptors (AR, ERα, ERβ, GRP30) and evaluation of epigenetic markers (EZH2). The results revealed that gerbils exposed to BPA exhibited increased body weight, alongside significant alterations in serum hormone profiles, including decreased cortisol and elevated estradiol levels. Furthermore, there was an upregulation of steroidogenic enzymes, indicating BPA's disruptive effects on adrenal hormone production and regulation. Notably, intracellular testosterone levels were elevated despite the typical age-related declines observed in control groups. Additionally, increased expression of androgen receptors and GPR30 was noted, underscoring BPA's complex impact on steroidogenic pathways. These findings emphasize the potential for intrauterine BPA exposure to induce enduring endocrine disturbances.