High Content Imaging Analyses of the Effects of Bisphenols and Organophosphate Esters on TM4 Mouse Sertoli Cells

Biol Reprod. 2022 May 20:ioac101. doi: 10.1093/biolre/ioac101. Online ahead of print.ABSTRACTThe endocrine disruptive effects of bisphenol A (BPA) and brominated flame retardants (BDE-47) have led to restrictions to their use and increased the pressure to identify safe replacements for these chemicals. Although there is evidence that some of these alternatives may be toxic to spermatogonial and Leydig cells, little is known about the toxicity of emerging replacements on Sertoli cells, one of the major testicular cell types. We used high-content imaging to compare the effects of legacy chemicals, BPA and BDE-47, to their corresponding replacements. TM4 Sertoli cells were exposed for 48 h to each chemical (0.001-100 μM) followed by cytotoxicity and phenotypic endpoint assessment. The benchmark concentration (BMC) potency ranking for bisphenols based on cytotoxicity was BPTMC>BPM > BPAF>BPF > BPS > BPA. Human administered equivalent dose (AED) determination ranked BPS as most potent alternative replacement studied. The BMC potency ranking of BDE-47 and organophosphate esters based on cytotoxicity was TDtBPP>BDMPP>TBOEP>TDCPP>TMPP>TPHP> BDE47 > IPPP=BPDP = TCPP. Additionally, TM4 cell exposure to BDE-47 increased Calcein intensity (57.9 μM) and affected lysosomes (21.6 μM), while exposure to TPHP and TMPP resulted in cellular oxidative stress changes at BMC values as low as 0.01 μM and 0.4 μM, respectively. Overall bioactivity consideratio...
Source: Biology of Reproduction - Category: Reproduction Medicine Authors: Source Type: research