2. Academic Validation
  3. Microcystin-LR induces lactate production disruption via altering the m6A modification in Sertoli cells

Microcystin-LR induces lactate production disruption via altering the m6A modification in Sertoli cells

  • Ecotoxicol Environ Saf. 2023 Jul 21;263:115288. doi: 10.1016/j.ecoenv.2023.115288.
Xiannan Meng 1,  Wenju Li 2,  Qingxuan Wu 1,  Yue Gao 1,  Ling Zhang 3
Affiliations

Affiliations

  • 1 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China.
  • 2 Department of Tropical Medicine and Infectious Diseases, Hainan Hospital, The Chinese PLA General Hospital, Sanya, Hainan, China.
  • 3 Cancer Institute, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China; Department of Histology and Embryology, Basic Medical College, Xuzhou Medical University, 209 Tongshan Road, Xuzhou, Jiangsu 221004, China. Electronic address: zhanglxy@xzhmu.edu.cn.
PMID: 37481861 DOI: 10.1016/j.ecoenv.2023.115288
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.

Keywords

Igf2bp3; Lactate dehydrogenase A; MC-LR; Methyltransferase 3; Testis.

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