Informace o publikaci
Lipid-disrupting effects of an organochlorine mixture in Sertoli TM4 cells reveal testicular obesogen mechanisms
| Autoři | |
|---|---|
| Rok publikování | 2026 |
| Druh | Recenzovaný odborný článek |
| Časopis / Zdroj | Archives of Toxicology |
| Fakulta / Pracoviště MU | |
| Citace | |
| www | https://link.springer.com/article/10.1007/s00204-026-04446-4 |
| Doi | https://doi.org/10.1007/s00204-026-04446-4 |
| Klíčová slova | Endocrine-disrupting chemicals; Lipidomics; Male reproductive toxicity; Mixture assessment; Obesogens; Organochlorines; Sertoli cells |
| Přiložené soubory | |
| Popis | Male reproductive health is declining globally, reflected by reduced sperm counts, impaired semen quality, increasing infertility, and a rising incidence of testicular cancer. Endocrine-disrupting chemicals include metabolic disruptors, within which obesogens represent a specific subgroup that dysregulate lipid metabolism and cellular energy homeostasis and are increasingly implicated in these adverse trends. Although obesogens act across multiple tissues, their lipid-metabolism-related effects on testicular cells remain comparatively understudied. We investigated male reprotoxicity of an environmentally and human-relevant organochlorine mixture (OC-MIX), consisting of 20 persistent contaminants, including polychlorinated biphenyls (PCBs), chlordane, and dichlorodiphenyltrichloroethane/dichlorodiphenyldichloroethane (DDT/DDE), originally identified in ringed seal blubber and representative of Arctic food-chain exposures. Although OC-MIX has shown male reproductive toxicity in animal models, its cellular mechanisms in Sertoli cells remain insufficiently defined. Using immature murine Sertoli TM4 cells, we demonstrated that OC-MIX (5-50 & micro;g/mL) disrupted lipid homeostasis and induced oxidative stress, culminating in lipotoxicity, processes known to compromise Sertoli cell support of spermatogenesis. These responses differed from those elicited by a fatty acid mixture or the lipotoxicant amiodarone and did not appear to involve androgen receptor, aryl hydrocarbon receptor, or peroxisome proliferator-activated alpha signaling, suggesting distinct lipid-centered mechanisms. Comparative profiling in immature murine Leydig TM3 cells revealed cell-type-specific responses, likely reflecting intrinsic differences in lipid composition. Notably, OC-MIX selectively altered phospholipid and lysophospholipid species in Sertoli TM4 cells, indicating interference with membrane remodeling and lipid-dependent signaling. Overall, these findings support the hypothesis that persistent organochlorines act as testicular obesogens, contributing to male reproductive dysfunction through selective, lipid-disrupting mechanisms. |
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