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Measuring Lactase Enzymatic Activity in the Teaching Lab
Published on: August 6, 2018
Microcystin-LR induces lactate production disruption via altering the m6A modification in Sertoli cells
Xiannan Meng1, Wenju Li2, Qingxuan Wu1
1Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China.
Abstract:
We have previously reported the toxicity of microcystin-LR (MC-LR) to the male reproductive system, which results in functional changes in mouse testes. In this study, mice were orally exposed to MC-LR at 1, 7.5, 15, or 30 μg/L daily for 180 days. We found an increase in germ cell apoptosis in the seminiferous tubules and low-quality sperm in the epididymis. A decrease in lactate dehydrogenase A (Ldha) expression in testes through high-throughput sequencing was observed. We validated that MC-LR disrupted lactate production in Sertoli cells by suppressing the expression of Ldha. Further studies identified that methyltransferase 3 (Mettl3) catalysed N6-methyladenosine (m6A) methylation of Ldha mRNA. Mettl3 was downregulated in Sertoli cells following exposure to MC-LR, decreasing m6A levels of Ldha. The stability of Ldha mRNA decreased when m6A levels of Ldha were inhibited. In conclusion, these results showed that MC-LR inhibits the expression of Ldha in an m6A-dependent manner, which might result in the apoptosis of spermatogenic cells and a decline in sperm quality. Our work provides a new perspective to understanding MC-LR-induced male infertility.
Insights
Microcystin-LR (MC-LR) exposure damages male fertility by reducing lactate dehydrogenase A (Ldha) expression. This epigenetic change, mediated by methyltransferase 3 (Mettl3), causes sperm damage and germ cell apoptosis.
Area of Science:
- Environmental Toxicology
- Reproductive Biology
- Epigenetics
Background:
- Microcystin-LR (MC-LR) is a cyanotoxin known to impair male reproductive function.
- Previous studies indicated functional changes in mouse testes following MC-LR exposure.
Purpose of the Study:
- To investigate the molecular mechanisms underlying MC-LR-induced male infertility.
- To explore the role of lactate dehydrogenase A (Ldha) and its regulation in MC-LR toxicity.
Main Methods:
- Mice were orally exposed to varying doses of MC-LR for 180 days.
- High-throughput sequencing was used to analyze gene expression changes in testes.
- The role of methyltransferase 3 (Mettl3) in regulating Ldha mRNA methylation (m6A) was investigated.
Main Results:
- MC-LR exposure led to increased germ cell apoptosis and reduced sperm quality.
- Lactate dehydrogenase A (Ldha) expression was significantly decreased in MC-LR-exposed testes.
- MC-LR downregulated Mettl3 in Sertoli cells, reducing Ldha mRNA m6A methylation and stability.
Conclusions:
- MC-LR inhibits Ldha expression in an m6A-dependent manner, contributing to male infertility.
- This epigenetic mechanism involving Mettl3 and Ldha impacts spermatogenic cell apoptosis and sperm quality.
- The findings offer a novel perspective on MC-LR-induced male reproductive toxicity.
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