Hatching enzymes disrupt aberrant gonadal degeneration by the autophagy/apoptosis cell fate decision

Sci Rep. 2017 Jun 9;7(1):3183. doi: 10.1038/s41598-017-03314-7.

Abstract

Environmental stressors, gonadal degenerative diseases and tumour development can significantly alter the oocyte physiology, and species fertility and fitness. To expand the molecular understanding about oocyte degradation, we isolated several spliced variants of Japanese anchovy hatching enzymes (AcHEs; ovastacin homologue) 1 and 2, and analysed their potential in oocyte sustenance. Particularly, AcHE1b, an ovary-specific, steroid-regulated, methylation-dependent, stress-responsive isoform, was neofunctionalized to regulate autophagic oocyte degeneration. AcHE1a and 2 triggered apoptotic degeneration in vitellogenic and mature oocytes, respectively. Progesterone, starvation, and high temperature elevated the total degenerating oocyte population and AcHE1b transcription by hyper-demethylation. Overexpression, knockdown and intracellular zinc ion chelation study confirmed the functional significance of AcHE1b in autophagy induction, possibly to mitigate the stress effects in fish, via ion-homeostasis. Our finding chronicles the importance of AcHEs in stress-influenced apoptosis/autophagy cell fate decision and may prove significant in reproductive failure assessments, gonadal health maintenance and ovarian degenerative disease therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Autophagy
  • Cell Lineage / genetics
  • DNA Fragmentation
  • Fertility / genetics
  • Gonads / chemistry*
  • Gonads / growth & development
  • Metalloendopeptidases / chemistry*
  • Metalloendopeptidases / genetics
  • Oocytes / chemistry*
  • Oocytes / growth & development
  • Progesterone / genetics
  • Protein Isoforms / chemistry
  • Protein Isoforms / genetics*
  • Proteolysis
  • Vertebrates / growth & development

Substances

  • Protein Isoforms
  • Progesterone
  • Metalloendopeptidases
  • envelysin