Perinatal Exposure to Bisphenol A and the Development of Prostatic Pre-neoplastic Lesions: A Systematic Review and Meta-analysis of Experimental Studies

Bisphenol A (BPA) is a widespread environmental endocrine disruptor that mimics steroid hormones, particularly estrogens, altering cellular function and potentially promoting carcinogenesis in hormone-sensitive organs such as the prostate. This systematic review and meta-analysis aimed to assess whether perinatal BPA exposure contributes to the development of pre-neoplastic prostatic lesions in adult male rats. Following PRISMA guidelines, we included preclinical studies investigating BPA exposure during the perinatal period and its effects on prostatic histopathology. Four studies met the inclusion criteria, evaluating the incidence and severity of lesions—such as prostatic intraepithelial neoplasia (PIN) and adenocarcinomas—in different prostatic lobes. The lateral lobe was consistently the most sensitive to BPA-induced PIN, particularly at low doses and when followed by hormonal stimulation in adulthood. Meta-analysis of three eligible studies revealed a pooled odds ratio of 20.25, indicating a significantly increased risk of developing PIN following perinatal BPA exposure. Notably, lower BPA doses (0.1–2.5 µg/kg) were associated with more severe lesions, suggesting a non-monotonic dose–response relationship. Perinatal exposure to BPA increases susceptibility to pre-neoplastic lesions in the prostate, particularly in the context of subsequent hormonal stimulation. These findings highlight the importance of regulatory measures to limit BPA exposure during critical windows of development.