2. Academic Validation
  3. Retinoic acid mitigates the NSC319726-induced spermatogenesis dysfunction through cuproptosis-independent mechanisms

Retinoic acid mitigates the NSC319726-induced spermatogenesis dysfunction through cuproptosis-independent mechanisms

  • Cell Biol Toxicol. 2024 May 1;40(1):26. doi: 10.1007/s10565-024-09857-6.
Haisheng Yi 1,  Tong Chen 2,  Guitian He 2,  Lingyun Liu 1,  Jiantao Zhao 1,  Kaimin Guo 1,  Yin Cao 1,  Penghao Sun 1,  Xu Zhou 3,  Boqi Zhang 4,  Chunjin Li 5,  Hongliang Wang 6
Affiliations

Affiliations

  • 1 Department of Andrology, The First Hospital of Jilin University, Jilin University, Changchun, 130012, China.
  • 2 College of Animal Sciences, Jilin University, Changchun, 130062, China.
  • 3 College of Animal Sciences, Jilin University, Changchun, 130062, China. zxu@jlu.edu.cn.
  • 4 College of Animal Sciences, Jilin University, Changchun, 130062, China. zzhangbq@jlu.edu.cn.
  • 5 College of Animal Sciences, Jilin University, Changchun, 130062, China. li_chunjin@jlu.edu.cn.
  • 6 Department of Andrology, The First Hospital of Jilin University, Jilin University, Changchun, 130012, China. hongliang@jlu.edu.cn.
PMID: 38691186 DOI: 10.1007/s10565-024-09857-6
Abstract

Copper ionophore NSC319726 has attracted researchers' attention in treating diseases, particularly cancers. However, its potential effects on male reproduction during medication are unclear. This study aimed to determine whether NSC319726 exposure affected the male reproductive system. The reproductive toxicity of NSC319726 was evaluated in male mice following a continuous exposure period of 5 weeks. The result showed that NSC319726 exposure caused testis index reduction, spermatogenesis dysfunction, and architectural damage in the testis and epididymis. The exposure interfered with spermatogonia proliferation, meiosis initiation, sperm count, and sperm morphology. The exposure also disturbed androgen synthesis and blood testis barrier integrity. NSC319726 treatment could elevate the copper ions in the testis to induce Cuproptosis in the testis. Copper chelator rescued the elevated copper ions in the testis and partly restored the spermatogenesis dysfunction caused by NSC319726. NSC319726 treatment also decreased the level of retinol dehydrogenase 10 (RDH10), thereby inhibiting the conversion of retinol to retinoic acid, causing the inability to initiate meiosis. Retinoic acid treatment could rescue the meiotic initiation and spermatogenesis while not affecting the intracellular copper ion levels. The study provided an insight into the bio-safety of NSC319726. Retinoic acid could be a potential therapy for spermatogenesis impairment in patients undergoing treatment with NSC319726.

Keywords

Adjuvant medication; Copper ionophore; Cuproptosis; NSC319726; Retinoic acid; Spermatogenesis dysfunction.

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