Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis

Abstract

WHAT IS KNOWN ALREADY:The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. STUDY DESIGN, SIZE, DURATION:Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB), and bisphenol A diglycidyl ether (BADGE) at 10 -9 to 10 -5 M for 24 h or 48h.PARTICIPANTS/MATERIALS, SETTING, METHODS: Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase 3 immunohistochemistry), and the levels of testosterone, insulin-like fator 3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). MAIN RESULTS AND THE ROLE OF CHANCE: A significant dose-dependent inhibition wasfound between testosterone levels measured in the culture medium and concentrations of BPA The active concentrations of BPA and BPA-A used in the study were higher than those found in human biological fluids. WIDER IMPLICATIONS OF THE FINDINGS:Under our experimental conditions, direct exposure to BPA or BPA-A can result in endocrine disturbance in the adult human testis.

Neuroendocrine disruption in animal models due to exposure to bisphenol A analogues

“…Several studies examining individuals living in the US and other countries detected measureable amounts of these BPA-substitutes in urinary samples, but mixed results have been reported in maternal sera, and umbilical cord sera (Table 1) [41; 42; 43; 44; 45; 46; 47; 48; 49; 50; 51]. These other bisphenols induce a range of gene expression and morphological changes in in vitro cultures of human explants and cells lines, such as testis, red blood cells, blood mononuclear cells, preadipocytes, cancerous adrenal cortex cells, and osteosarcoma cells [52; 53; 54; 55; 56; 57; 58; 59; 60]. …”

Mechanisms of Testicular Disruption from Exposure to Bisphenol A and Phtalates

“…Leydig cell production of INSL3 was increased after exposure to BPA, bisphenol B and S, and reduced after exposure to bisphenol E; both effects were dose-dependent. In contrast, Sertoli cell activity as measured by INHB levels was unchanged [97]. The more conflicting results than animal models can be in part explained by the known concept of species differences in BPA response among animal models can be broadened to humans as well, especially because human exposure in vivo differs greatly from the setting of controlled experiments, implying lower levels of overall BPA contaminations but arising from multiple exposure routes; furthermore, these papers investigated only urinary BPA, while it is now accepted that simultaneous contamination of mixtures if EDCs may mediate most of the reproductive alterations.…”

Challenges to regulate products containing bisphenol A: Implications for policy

“…31 More recently, it has also been documented in experimental studies that these compounds may decrease basal testosterone secretion by human fetal and adult testes, induce oxidative stress in human red blood cells and change cancer-related genes methylation profiles in human breast cancer cells. 2,[32][33][34] Even though these findings warrant confirmation, current packaging labeled as BPA-free, likely contains BPS and BPF which may be just as harmful. Other materials like polyesters, polypropylenes, and acrylics may be safer compounds and have started to replace BPA-containing polycarbonate in baby bottles.…”