Effects of bisphenols on Blood-Testis Barrier protein expression in vitro: A systematic review and meta-analysis.

Bisphenols are a group of environmental endocrine-disrupting chemicals that produce alterations in the expression of intercellular junction proteins of the Blood-Testis Barrier (BTB) involved in spermatogenesis. The association between bisphenol exposure and BTB protein expression is controversial. Therefore, we performed this systematic review and meta-analysis to clarify bisphenol effects on Sertoli cell BTB protein expression in vitro. The Standardized Mean Difference (SMD) with a 95 % confidence interval (95 % CI) was used to evaluate the association between alterations in the BTB protein expression and bisphenol exposure in vitro. Six articles were included in the meta-analysis. Bisphenol-A (BPA) exposure at 200 µM was associated with significant decrease in BTB protein expression (SMD = -2.70, 95 %CI: -3.59, -1.80, p het = 0.46, p = <0.00001). In the moderate (40-50 µM) and low dose (<25 µM), no significant associations were obtained. We also found a non-monotonic dose-response curve of bisphenol effect in ZO-1 protein expression; low and high doses presented a significant decrease compared to control, while moderate dose presented no change. The current temporary Tolerable Daily Intake (tTDI) of BPA is 4 µg/kg bw/day. The 5-25 µM doses of BPA are equivalent to ∼1-5 mg/kg bw, respectively. Although the low dose group (<25 µM) assessed doses below the previous NOAEL value, these doses are above the current tTDI. Thus, it is necessary to conduct more studies with lower bisphenol concentrations to avoid underestimating the potential adverse effects of bisphenols at doses below tTDI.