Disrupting mitochondrial function with surfactants inhibits MA-10 Leydig cell steroidogenesis

Abstract

It is well established that surfactants can elicit cytotoxic effects at threshold concentrations by changing the permeability and solubilizing components of cell membranes. The purpose of this study was to characterize the relationship between perturbation of the mitochondrial membrane resulting from treatment with representative cationic, nonionic, and anionic surfactants and the extent to which this perturbation affects steroid formation and StAR protein expression and activity in MA-10 Leydig cells. The StAR protein is synthesized as an active 37 kDa extramitochondrial form, which is processed into a 30 kDa intramitochondrial form after cholesterol transfer and mitochondrial import and processing. It has been shown in several in vitro studies that the mitochondrial electrochemical gradient is required for the StAR protein to transfer cholesterol to the inner mitochondrial membrane. Each substance that was tested produced a concentration-dependent decrease in steroid formation in hCG-stimulated MA-10 cells. Decreases in progesterone production were accompanied by loss of mitochondrial membrane potential and by a decrease in the levels of the 30 kDa form of the StAR protein. However, levels of the 37 kDa form of the StAR protein did not decrease, indicating no effect on StAR protein expression. These results demonstrate how perturbation of the mitochondrial membrane by surfactants inhibits import, processing, and cholesterol transfer activity and underscore the importance of including sensitive assays that evaluate mitochondrial function when screening for potential effects on steroidogenesis with in vitro test systems.

Aquatic hazard assessment of MON 0818, a commercial mixture of alkylamine ethoxylates commonly used in glyphosate‐containing herbicide formulations. Part 1: Species sensitivity distribution from laboratory acute exposures

“…This narrow range is particularly apparent for the fish species (0.83–1.74 mg MON 0818 L −1 ), most likely indicating a similar mechanism of action across animal species. Narcotic effect–induced membrane damage in the gill epithelium has been suggested as a potential mechanism of action , which is consistent with the surfactant properties of POEAs. In addition, the absolute difference for individual species between their estimated EC10s and EC90s was narrow, suggesting the existence of a threshold concentration.…”

“…In addition, the absolute difference for individual species between their estimated EC10s and EC90s was narrow, suggesting the existence of a threshold concentration. The existence of this threshold has been noted in previous studies , where it has been associated with the critical micelle concentration (the concentration at which micelles start forming on a solution of surfactant) for MON 0818 and similar POEA mixtures in water. The critical micelle concentration measured in these studies was 1 mg to 3 mg MON 0818 L −1 .…”

Review of genotoxicity studies of glyphosate and glyphosate-based formulations

“…As a more specific example, polyoxyethylenealkalylmine (POEA), a surfactant component of some GBFs, has been shown to elicit cytotoxic effects such as perturbation of the mitochondrial membrane and disruption of mitochondrial membrane potential in cultured mammalian cells (Levine et al, 2007). Surfactant effects provide a very plausible mechanism for observations of GBFs inducing DNA damage responses.…”

Gonadotropin-releasing hormone positively regulates steroidogenesis via extracellular signal-regulated kinase in rat Leydig cells

“…MA-10 Leydig tumour cells have been used extensively to study many of the functions of Leydig cells. [25][26][27][28] . However, the primary culture system employed in this study more closely resembles the cells in vivo.…”