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The possibility of chemical contamination is an important issue to consider when designing a cell therapy strategy. Both bisphenol A (BPA) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are among the most environmentally relevant endocrine disrupting chemicals (EDCs, compounds with a high affinity for adipose tissue) recently studied. Adipose-derived stem cells (ASCs) are mesenchymal stromal cells (MSCs) obtained from adipose tissue widely used in regenerative medicine to prevent and treat diseases in several tissues and organs. Although the experimental use of tissue-engineered constructs requires careful analysis for approval and implantation, there has been a recent increase in the number of approved clinical trials for this promising strategy. This study aimed to evaluate cell viability, apoptosis, DNA damage, and the adipogenic or osteogenic differentiation potential of rat adipose-derived stem cells (rASCs) exposed to previously established non-cytotoxic doses of BPA and TCDD in vitro. Results demonstrated that 10 μM of BPA and 10 nM of TCDD were able to significantly reduce cell viability, while all exposure levels resulted in DNA damage, although did not increase the apoptosis rate. According to the analysis of adipogenic differentiation, 1 μM of BPA induced the significant formation of oil droplets, suggesting an increased adipocyte differentiation, while both 10 μM of BPA and 10 nM of TCDD decreased adipocyte differentiation. Osteogenic differentiation did not differ among the treatments. As such, BPA and TCDD in the concentrations tested can modify important processes in rASCs such as cell viability, adipogenic differentiation, and DNA damage. Together, these findings prove that EDCs play an important role as contaminants, putatively interfering in cell differentiation and thus impairing the therapeutic use of ASCs.

Parabens are hormonally active chemicals widely used as preservatives in foods and are frequently detected in human fluids and tissues. Therefore, the objective of this study was to determine the effects of maternal butyl paraben (BP) exposure on male sexual development. Pregnant Wistar rats received corn oil (control group), or BP at doses of 10, 100, or 200 mg/kg, subcutaneously, from gestational day 12 until postnatal day 21. Our results demonstrated that developmental BP exposure significantly increased the number of adult Leydig cells and the circulating concentrations of testosterone and attenuated FSH and LH concentrations at 200 mg/kg. BP exposure adversely affected spermatogenesis kinetics at doses of 10 and 200 mg/kg and provoked a decrease in the immunostaining of EsR1 and AR at 200 mg/kg. The sperm motility was impaired at the 10 mg/kg dose, and sperm head abnormalities were increased in all BP dose groups. We suggest that BP impairs testicular structure and function in the rat, affecting sperm quality. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1273–1289, 2017.