Upregulated microRNA-423-5p promotes oxidative stress through targeting glutathione S-transferase mu 1 in

Rongxue Zhang1, Yanghua Zuo1, Senyang Cao1

  • 1Center of Reproductive Medicine, Huai'an Maternity and Child Health Care Center, Huai'an, China.

Insights

Sperm microRNA-423-5p (miR-423-5p) is upregulated in asthenozoospermia, negatively impacting sperm motility. This microRNA (miRNA) targets GSTM1, increasing oxidative stress and reducing sperm function.

Area of Science:

  • Reproductive Biology
  • Molecular Biology
  • Biochemistry

Background:

  • MicroRNA (miRNA) dysregulation is implicated in asthenozoospermia, a condition characterized by impaired sperm motility.
  • Specific miRNAs, such as microRNA-423-5p (miR-423-5p), are being investigated for their roles in male infertility.

Purpose of the Study:

  • To evaluate sperm miR-423-5p expression in asthenozoospermia versus normozoospermia.
  • To explore the diagnostic potential of miR-423-5p in asthenozoospermia.
  • To elucidate the molecular mechanism of miR-423-5p action in asthenozoospermia.

Main Methods:

  • Quantitative Real-Time polymerase chain reaction (qRT-PCR) to measure sperm miR-423-5p levels.
  • Receiver operating characteristic (ROC) curve analysis to assess diagnostic accuracy.
  • Dual-reporter luciferase assay to identify miR-423-5p targets.
  • Measurement of target gene expression (GSTM1) and oxidative stress markers (GST activity, TAC, MDA).

Main Results:

  • Sperm miR-423-5p levels were significantly higher in asthenozoospermic (AZS) individuals compared to normozoospermic (Norm) individuals.
  • ROC analysis indicated miR-423-5p has moderate diagnostic value for asthenozoospermia (AUC=0.69).
  • Glutathione S-transferase mu 1 (GSTM1) was identified as a direct target of miR-423-5p, with decreased expression in AZS.
  • Elevated miR-423-5p correlated with reduced sperm motility, decreased GST activity and total antioxidant capacity (TAC), and increased malondialdehyde (MDA) levels, indicating increased oxidative stress.

Conclusions:

  • Sperm miR-423-5p is significantly upregulated in asthenozoospermia.
  • miR-423-5p may inhibit sperm motility by targeting GSTM1, thereby promoting oxidative stress.
  • miR-423-5p represents a potential biomarker and therapeutic target for asthenozoospermia.