Regulation of cell death in human fetal and adult ovaries--role of Bok and Bcl-X(L)

Mol Cell Endocrinol. 2010 Dec 15;330(1-2):17-24. doi: 10.1016/j.mce.2010.07.020. Epub 2010 Jul 29.

Abstract

Of eight million oocytes formed in fetal ovaries, only 400 are ovulated and the rest are degraded via apoptosis. Studies in rodents suggest an important role for Bok and Bcl-X(L) in ovarian apoptosis, but their expression patterns and roles in human ovaries are not well known. Protein expression of Bok and Bcl-X(L) as well as the death pathway effectors TNF and caspase-3 were determined in an important collection of samples consisting of human fetal and adult ovaries. A penetrant expression of Bok, Bcl-X(L), TNF and full length and cleaved caspase-3 were characterized in fetal ovaries, with specific patterns in oocytes and pre-granulosa/granulosa cells. Bok and Bcl-X(L) were detected also in adult ovaries. Lentiviral shRNA delivery demonstrated that loss of Bok markedly reduces vulnerability to apoptosis and, conversely, loss of Bcl-X(L) increases apoptosis in human granulosa tumour cell line. The results suggest important roles for Bok and Bcl-X(L) in human ovarian development, follicle maturation and apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blotting, Western
  • Caspase 3 / metabolism
  • Cell Death
  • Cytoprotection
  • Enzyme Activation
  • Female
  • Granulosa Cells / metabolism
  • Granulosa Cells / pathology
  • Humans
  • Middle Aged
  • Ovary / cytology*
  • Ovary / enzymology
  • Ovary / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism
  • bcl-X Protein / metabolism*

Substances

  • BOK protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • bcl-X Protein
  • Caspase 3