Real-life organochlorine mixture-induced lipid dysregulation
and oxidative stress in Leydig TM3 cells: Mechanistic insights
into male reprotoxicity

J 2026

Real-life organochlorine mixture-induced lipid dysregulation and oxidative stress in Leydig TM3 cells: Mechanistic insights into male reprotoxicity

VIRMANI, Ishita; Eliška SYCHROVÁ; Eliška ŘEHŮŘKOVÁ; Darshak Chandulal GADARA; Zdeněk SPÁČIL et al.

Základní údaje

Originální název

Real-life organochlorine mixture-induced lipid dysregulation and oxidative stress in Leydig TM3 cells: Mechanistic insights into male reprotoxicity

Autoři

VIRMANI, Ishita; Eliška SYCHROVÁ ; Eliška ŘEHŮŘKOVÁ ; Darshak Chandulal GADARA; Zdeněk SPÁČIL; Jiří NOVÁK a Iva SOVADINOVÁ

Vydání

Toxicology, Clare, Ireland, Elsevier Sci Ireland Ltd, 2026, 0300-483X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30108 Toxicology

Stát vydavatele

Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 4.600 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

Endocrine-disrupting chemicals; Environmental mixture; Leydig TM3 cells; Lipidomics; Organochlorines; Reproductive toxicity

Štítky

143180, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 3. 2026 12:07, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

Persistent environmental pollutants such as organochlorines (OCs) remain a global concern due to their widespread distribution, bioaccumulative nature, and endocrine-disrupting potential. While associations with male reproductive toxicity are well documented, the underlying mechanisms, particularly those involving lipid metabolism in testicular cells, are not fully understood. This study investigates the mechanistic basis of male reprotoxicity induced by a real-life OC mixture (OC-MIX), modeled after the contaminant profile of ringed seal blubber and comprising 20 environmentally relevant OCs, including pesticides (e.g., dichlorodiphenyltrichloroethane) and industrial compounds (e.g., polychlorinated biphenyls). We applied a mechanistic in vitro test battery that combines receptor-specific reporter gene assays with functional profiling in immature murine Leydig TM3 cells exposed to OC-MIX concentrations ranging from 0.04 to 50 mu g/mL. OC-MIX exhibited strong antiandrogenic and dioxin-like activities. Functional assays revealed reduced testosterone and progesterone levels, increased oxidative stress, and impaired mitochondrial function. These effects were driven by broad lipid dysregulation, including enhanced fatty acid degradation and acylcarnitine depletion, which was evident even at the lowest tested concentration (2.5 mu g/mL). These lipid alterations were not primarily mediated via androgen receptor antagonism or aryl hydrocarbon receptor agonism. Instead, the lipidomic signature closely resembled that of the lipotoxic drug amiodarone, rather than a non-cytotoxic fatty acid mixture. Our findings underscore the central role of lipid metabolism in testicular function and demonstrate that OC-MIX exerts reproductive toxicity via complex, non-classical endocrine mechanisms. This study highlights the value of integrating lipidomics with mechanistic in vitro models to assess the reproductive toxicity of environmental chemical mixtures.

Návaznosti

EF17_043/0009632, projekt VaV

Název: CETOCOEN Excellence

EF19_073/0016943, projekt VaV

Název: Interní grantová agentura Masarykovy univerzity

GA22-30004S, projekt VaV

Název: Alternativní přístupy v hodnocení mužské reprodukční toxicity chemických směsí bez využití zvířat

Investor: Grantová agentura ČR, Alternativní přístupy v hodnocení mužské reprodukční toxicity chemických směsí bez využití zvířat

LM2023069, projekt VaV

Název: Výzkumná infrastruktura RECETOX

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

Citovat

VIRMANI, Ishita; Eliška SYCHROVÁ; Eliška ŘEHŮŘKOVÁ; Darshak Chandulal GADARA; Zdeněk SPÁČIL; Jiří NOVÁK a Iva SOVADINOVÁ. Real-life organochlorine mixture-induced lipid dysregulation and oxidative stress in Leydig TM3 cells: Mechanistic insights into male reprotoxicity. Toxicology. Clare, Ireland: Elsevier Sci Ireland Ltd, 2026, roč. 519, January 2026, s. 1-12. ISSN 0300-483X. Dostupné z: https://doi.org/10.1016/j.tox.2025.154332.

@article{2559460,
   author = {Virmani, Ishita and Sychrová, Eliška and Řehůřková, Eliška and Gadara, Darshak Chandulal and Spáčil, Zdeněk and Novák, Jiří and Sovadinová, Iva},
   article_location = {Clare, Ireland},
   article_number = {January 2026},
   doi = {https://doi.org/10.1016/j.tox.2025.154332},
   keywords = {Endocrine-disrupting chemicals; Environmental mixture; Leydig TM3 cells; Lipidomics; Organochlorines; Reproductive toxicity},
   language = {eng},
   issn = {0300-483X},
   journal = {Toxicology},
   title = {Real-life organochlorine mixture-induced lipid dysregulation and oxidative stress in Leydig TM3 cells: Mechanistic insights into male reprotoxicity},
   url = {https://www.sciencedirect.com/science/article/pii/S0300483X25002914},
   volume = {519},
   year = {2026}
}

TY  - JOUR
ID  - 2559460
AU  - Virmani, Ishita - Sychrová, Eliška - Řehůřková, Eliška - Gadara, Darshak Chandulal - Spáčil, Zdeněk - Novák, Jiří - Sovadinová, Iva
PY  - 2026
TI  - Real-life organochlorine mixture-induced lipid dysregulation and oxidative stress in Leydig TM3 cells: Mechanistic insights into male reprotoxicity
JF  - Toxicology
VL  - 519
IS  - January 2026
SP  - 1-12
EP  - 1-12
PB  - Elsevier Sci Ireland Ltd
SN  - 0300483X
KW  - Endocrine-disrupting chemicals
KW  - Environmental mixture
KW  - Leydig TM3 cells
KW  - Lipidomics
KW  - Organochlorines
KW  - Reproductive toxicity
UR  - https://www.sciencedirect.com/science/article/pii/S0300483X25002914
N2  - Persistent environmental pollutants such as organochlorines (OCs) remain a global concern due to their widespread distribution, bioaccumulative nature, and endocrine-disrupting potential. While associations with male reproductive toxicity are well documented, the underlying mechanisms, particularly those involving lipid metabolism in testicular cells, are not fully understood. This study investigates the mechanistic basis of male reprotoxicity induced by a real-life OC mixture (OC-MIX), modeled after the contaminant profile of ringed seal blubber and comprising 20 environmentally relevant OCs, including pesticides (e.g., dichlorodiphenyltrichloroethane) and industrial compounds (e.g., polychlorinated biphenyls). We applied a mechanistic in vitro test battery that combines receptor-specific reporter gene assays with functional profiling in immature murine Leydig TM3 cells exposed to OC-MIX concentrations ranging from 0.04 to 50 mu g/mL. OC-MIX exhibited strong antiandrogenic and dioxin-like activities. Functional assays revealed reduced testosterone and progesterone levels, increased oxidative stress, and impaired mitochondrial function. These effects were driven by broad lipid dysregulation, including enhanced fatty acid degradation and acylcarnitine depletion, which was evident even at the lowest tested concentration (2.5 mu g/mL). These lipid alterations were not primarily mediated via androgen receptor antagonism or aryl hydrocarbon receptor agonism. Instead, the lipidomic signature closely resembled that of the lipotoxic drug amiodarone, rather than a non-cytotoxic fatty acid mixture. Our findings underscore the central role of lipid metabolism in testicular function and demonstrate that OC-MIX exerts reproductive toxicity via complex, non-classical endocrine mechanisms. This study highlights the value of integrating lipidomics with mechanistic in vitro models to assess the reproductive toxicity of environmental chemical mixtures.
ER  -

VIRMANI, Ishita; Eliška SYCHROVÁ; Eliška ŘEHŮŘKOVÁ; Darshak Chandulal GADARA; Zdeněk SPÁČIL; Jiří NOVÁK a Iva SOVADINOVÁ. Real-life organochlorine mixture-induced lipid dysregulation and oxidative stress in Leydig TM3 cells: Mechanistic insights into male reprotoxicity. \textit{Toxicology}. Clare, Ireland: Elsevier Sci Ireland Ltd, 2026, roč.~519, January 2026, s.~1-12. ISSN~0300-483X. Dostupné z: https://doi.org/10.1016/j.tox.2025.154332.

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