1. Academic Validation
  2. 2,5-Hexanedione influences primordial follicular development in cultured neonatal mouse ovaries by interfering with the PI3K signaling pathway via miR-214-3p

2,5-Hexanedione influences primordial follicular development in cultured neonatal mouse ovaries by interfering with the PI3K signaling pathway via miR-214-3p

  • Toxicol Appl Pharmacol. 2020 Dec 15;409:115335. doi: 10.1016/j.taap.2020.115335.
Jingwen Zeng 1 Yan Sun 2 Xiaoqin Li 1 Jianlin Zhu 1 Wenchang Zhang 1 Wenmin Lu 1 Yuyao Weng 1 Jin Liu 3
Affiliations

Affiliations

  • 1 Department of Preventive Medicine, School of Public Health, Fujian Medical University, Xueyan Road No. 1, Minhou County, Fuzhou 350108, China.
  • 2 Reproductive Medicine Center, Fujian Provincial Maternity and Children's Hospital, Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
  • 3 Department of Preventive Medicine, School of Public Health, Fujian Medical University, Xueyan Road No. 1, Minhou County, Fuzhou 350108, China. Electronic address: [email protected].
Abstract

The mechanisms by which 2,5-hexanedione (2,5-HD) exposure adversely affects reproduction are unclear. In the present study, whole neonatal mouse ovaries were exposed to 2,5-HD in vitro and then assessed for progesterone levels to determine the effects of this compound on ovary function. Ovarian histomorphological analyses were performed to assess the effects of 2,5-HD on follicular development, and PI3K signaling pathway was evaluated to elucidate the molecular mechanisms of 2,5-HD-mediated toxicity on follicular development. The results showed that after ovarian exposure to 2,5-HD in vitro, the percentage of secondary follicles decreased, while the progesterone levels and the percentage of unhealthy follicles increased, with oocytes identified as the target of damage. The 2,5-HD treatment significantly decreased the of the gene encoding the apoptosis-related protein Caspase-8, and PI3K/Akt/FOXO3 pathway signaling was also altered. Furthermore, the effects of 2,5-HD on the gene expression of the PI3K/Akt/FOXO3 and follicular development were blocked by 740Y-P (a PI3K Activator), miR-214-3p was abnormally expressed, and luciferase reporter assay results demonstrated that the 3' untranslated region of PI3K was a direct target of miR-214-3p. Overall, the results of the present study indicate that 2,5-HD exposure inhibits follicular development, and the underlying mechanism may involve interference with miR-214-3p-mediated regulation of the PI3K signaling pathway.

Keywords

2,5-Hexanedione; Follicular development; PI3K signaling pathway; microRNAs.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P0175
    99.67%, PI3K Activator