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Published on: March 6, 2018
PBA alleviates cadmium-induced mouse spermatogonia apoptosis by suppressing endoplasmic reticulum stress
Rong Wang1, Mengyuan Li2, Zhen Wu3
1Department of health inspection and quarantine, School of Public Health, Anhui Medical University, Hefei, Anhui, China; Department of Histology and Embryology, Anhui Medical University, Hefei, China.
Objective:
Endoplasmic reticulum (ER) stress mediates Cd-caused germ cell apoptosis in testis. The effects of 4-phenylbutyric acid (PBA), a classical chaperone, were investigated on Cd-induced apoptosis in mouse GC-1 spermatogonia cells.
Methods:
The cells were pretreated with PBA before Cd exposure. TUNEL and flow cytometry assays were applied to determine apoptosis. Some key biomarkers of ER stress were analyzed using RT-PCR and western blot.
Results:
as expected, the apoptotic cells exposed to Cd apparently increased. The mRNA and protein expression levels of GRP78 and ATF6α, were elevated in the Cd groups. Additional experiments displayed that Cd notably increased IRE1α and JNK phosphorylation, and upregulated XBP-1 mRNA and protein expression. Moreover, p-eIF2α and CHOP expressions were clearly elevated in the Cd groups. Interestingly, PBA almost completely inhibited ER stress and protected spermatogonia against apoptosis induced by Cd.
Conclusion:
PBA alleviated Cd-induced ER stress and spermatogonia apoptosis, and may have the therapeutic role in Cd-induced male reproductive toxicity.
Insights
4-phenylbutyric acid (PBA) protects mouse spermatogonia cells from cadmium-induced apoptosis by alleviating endoplasmic reticulum (ER) stress. This study highlights PBA
Area of Science:
- Reproductive Toxicology
- Cell Biology
- Molecular Biology
Background:
- Cadmium (Cd) exposure induces germ cell apoptosis in the testis.
- Endoplasmic reticulum (ER) stress is a key mediator of Cd-induced testicular damage.
Purpose of the Study:
- To investigate the protective effects of 4-phenylbutyric acid (PBA) against Cd-induced apoptosis in mouse GC-1 spermatogonia cells.
- To elucidate the role of ER stress in Cd-induced spermatogonia apoptosis and the potential therapeutic effect of PBA.
Main Methods:
- GC-1 spermatogonia cells were pretreated with PBA before Cd exposure.
- Apoptosis was assessed using TUNEL and flow cytometry.
- ER stress biomarkers (GRP78, ATF6α, IRE1α, JNK, XBP-1, p-eIF2α, CHOP) were analyzed via RT-PCR and western blot.
Main Results:
- Cd exposure significantly increased spermatogonia apoptosis and elevated ER stress markers (GRP78, ATF6α, IRE1α, JNK phosphorylation, XBP-1, p-eIF2α, CHOP).
- PBA pretreatment markedly reduced Cd-induced apoptosis.
- PBA effectively inhibited ER stress pathways, protecting spermatogonia from Cd toxicity.
Conclusions:
- PBA alleviates Cd-induced ER stress and spermatogonia apoptosis.
- PBA demonstrates therapeutic potential for mitigating Cd-induced male reproductive toxicity.
