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Inulin Mitigates Reproductive Toxicity from Early Life GenX Exposure in Mice by Inhibiting LPS-TLR4-Mediated
Mei-Ting Zhong1, Ming-Quan Lai1, Ya-Qi Chen1
1Department of Toxicology, School of Public Health, Southern Medical University (Guangdong Provincial Key Laboratory of Tropical Disease Research), No. 1838 North Guangzhou Road, Guangzhou 510515, China.
Environment & Health (Washington, D.C.)
|May 21, 2026
Summary
Early-life exposure to GenX chemical in mice disrupts male reproductive development by causing gut imbalance and testicular injury. Inulin, a prebiotic, may protect against these harmful effects.
Area of Science:
- Environmental Science
- Toxicology
- Reproductive Biology
Background:
- Hexafluoropropylene oxide dimer acid (HFPO-DA or GenX) is a replacement for PFOA, but its effects on male reproductive development are not fully understood.
- Early-life exposure to environmental toxins can have long-lasting impacts on development and health.
Purpose of the Study:
- To investigate the effects of early-life GenX exposure on male reproductive development in mice.
- To explore the potential protective role of inulin, a prebiotic, against GenX-induced reproductive toxicity.
Main Methods:
- Pregnant mice were exposed to GenX and/or inulin during gestation and lactation.
- Male offspring were assessed at 16 weeks for gut microbiota, colonic and testicular histology, hormone levels, sperm quality, and gene expression related to inflammation and necroptosis.
- Transcriptomic analysis was performed on testicular tissue.
Main Results:
- GenX exposure led to gut dysbiosis, colonic inflammation, reduced tight junction proteins, increased serum LPS, testicular damage, decreased testosterone, impaired blood-testis barrier, and increased sperm abnormalities.
- GenX-induced testicular injury involved necroptosis, indicated by altered expression of RIPK1, RIPK3, TLR4, and caspase-8.
- Inulin administration ameliorated GenX-induced gut and testicular damage by modulating the LPS-TLR4-mediated necroptosis pathway.
Conclusions:
- Early-life GenX exposure poses a significant risk to male reproductive development through gut-testis axis disruption and necroptosis.
- Inulin shows potential as a dietary intervention to mitigate GenX-induced reproductive toxicity.
