Reproductive toxicity of emerging plasticizers, flame retardants, and bisphenols, using culture of the rat fetal testis

Abstract

The use of bis (2-ethylhexyl) phthalate (DEHP), 2,2′4,4′-tetrabromodiphenyl ether (BDE-47) and bisphenol A (BPA), as plasticizers, flame-retardant and epoxy resins, respectively, has been regulated due to their endocrine disrupting chemical (EDC) activities. Replacements for these chemicals are found in the environment and human matrices, yet the EDC activity of these emerging contaminants is poorly characterized. We compared the effects of legacy chemicals with those of their replacements using fetal rat testis organ culture. Fetal testes sampled at gestation day 15 were grown ex vivo and the impact was evaluated after a 3-day exposure to 10 μM of each legacy chemical, two BPA analogs (BPM and BPTMC), three replacements for DEHP/MEHP (TXIB, DINP, DIDA) or two replacements for BDE-47 (TBEP, IPPP). Using culture media, we showed that only BPA and MEHP significantly decrease basal testosterone secretions after 24 h of treatment while BPM and BPTMC have the opposite effect. LH-stimulated testosterone was reduced by BPA and MEHP but increased by BPTMC. After exposure, testes were used for immunofluorescent staining of germ cells, Sertoli cells and Leydig cells. Interestingly, the effect of BPM and BPTMC on testosterone secretion was associated with a significant increase in Leydig cell density and surface area. A decrease in germ cell density was observed only after treatment with MEHP or BDE-47. MEHP significantly decreased Sertoli cell proliferation. These studies show that some replacement chemicals can affect testicular function while others appear to show little toxicity in this model. These findings provide essential information regarding the need for their regulation.

An Investigation of the Protective Influence of Dates Fruit Against Nephrotoxicity in Wistar Albino Rats Induced by Gentamicin

“…The compound, 9,12-octadecadienoic acid (Z,Z)- [40]are predicted to be potent inhibitors of S. mansoni, P. falciparum, and T. brucei brucei survival, respectively. As a result, in vitro and in vivo bioassay studies on these compounds are required to establish the predictions [41].Cycloeicosane has antioxidant, cytotoxic, antibacterial, anti-candidiasis, and in vivo anti-inflammatory properties [42]. Octadecane has been shown to reduce apoptotic cells [43].…”

Bisphenol TMC disturbs mitochondrial activity and biogenesis, reducing lifespan and healthspan in the nematodeCaenorhabditis elegans

“…Due to its structural similarity to other harmful bisphenols and its growing presence in everyday products, further research on BPTMC has emerged to assess its potential toxicity. Several recent studies have highlighted the potential endocrine-disrupting and toxic effects of BPTMC 9, 10 . Recent research in Oryzias melastigma , a fish species, demonstrates detrimental developmental, behavioral, and endocrine effects following exposure to the chemical compound BPTMC 9 .…”

“…Furthermore, results from both in silico and in vitro experiments using Saccharomyces cerevisiae suggest that BPTMC strongly binds to the estrogen receptor 9 . Additionally, exposure to BPTMC has been shown to stimulate testosterone secretion in the culture of the rat fetal testis, suggesting potential endocrine-disrupting activity 10 . In vitro , assays also report that BPTMC can affect lipid droplet numbers in cultured MA-10 and KGN cells 11 .…”

“…Several recent studies have highlighted the potential endocrine-disrupting and toxic effects of BPTMC 9,10 . Recent research in Oryzias melastigma, a fish species, demonstrates detrimental developmental, behavioral, and endocrine effects following exposure to the chemical compound BPTMC 9 .…”