Stra8 may inhibit apoptosis during mouse spermatogenesis via the AKT signaling pathway.

Abstract

Stimulated by retinoic acid 8 (Stra8), one of genes induced by retinoic acid (RA), is required for the meiotic initiation of male spermatogenesis. The present study found that Stra8 inhibited apoptosis in male Stra8‑knockout mice, and in mice with vitamin A deficiency and vitamin A recovery in vivo. This phenotype was also verified in GC1 spermatogonia (spg) cells overexpressing Stra8. In addition, microarray analysis identified that there were nine differentially expressed genes (DEGs) in the Stra8‑overexpressed GC1 spg cells compared with the control groups; the expression of these nine genes was verified via mRNA expression levels. The DEGs were as follows: Phosphatidylinositol‑dependent kinase 1 (PDK1), a key gene upstream of protein kinase B (AKT); angiopoietin 2, a B‑cell lymphoma 2 (Bcl‑2)‑inhibited gene; transcription factor 4, glutathione S‑transferase P91 and ubiquitin‑specific protease 33, mitogen‑activated protein kinase (MAPK)‑related genes; oxidative stress induced growth inhibitor 1, related to the P53 pathway; Bcl‑2, P53, ERK (MAPK1/3), c‑Jun N‑terminal kinase (MAPK8/9), and P38 (MAPK14), all of which are key genes involved in the AKT signaling pathway. Therefore, the present study further verified these genes and found that the mRNA and protein expression levels of PDK1, AKT, Bcl‑2 and ERK were increased. Although the mRNA expression level of P53 was decreased, there was no significant difference in the protein expression level in Stra8‑overexpressing GC1 spg cells compared with controls. In addition, Caspase 3, one of the executioner caspases, was decreased in Stra8‑overexpressing GC1 spg cells compared with the control groups. Therefore, it was suggested that Stra8 may directly or indirectly inhibit caspases through the AKT signaling pathway and ultimately exert an anti‑apoptotic effect in the male reproductive system.

• Authors: Xueyi Shen, Changmin Niu, Jiaqian Guo, Mengmeng Xia, Jing Xia, Yanqiu Hu, Ying Zheng
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 42 Issue 5 Pg. 2819-2830 (Nov 2018) ISSN: 1791-244X [Electronic] Greece
• PMID: 30106128 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Angiopoietin-2
• Stra8 protein, mouse
• Transcription Factor 4
• 3-Phosphoinositide-Dependent Protein Kinases
• Pdpk1 protein, mouse
• Proto-Oncogene Proteins c-akt

Topics

• 3-Phosphoinositide-Dependent Protein Kinases (genetics)
• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Angiopoietin-2 (metabolism)
• Animals
• Apoptosis (genetics, physiology)
• Blotting, Western
• Cells, Cultured
• Female
• Male
• Mice
• Mice, Knockout
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• Signal Transduction (genetics, physiology)
• Spermatogenesis (genetics, physiology)
• Transcription Factor 4 (metabolism)