Regulation of cell death in human fetal and adult ovaries--role of Bok and Bcl-X(L).
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.
Jääskeläinen
Minna
M
Department of Obstetrics and Gynaecology, University of Oulu, Finland.
Nieminen
Anni
A
Pökkylä
Reeta-Maria
RM
Kauppinen
Marjut
M
Liakka
Annikki
A
Heikinheimo
Markku
M
Vaskivuo
Tommi E
TE
Klefström
Juha
J
Tapanainen
Juha S
JS
D000328:Adult; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D019610:Cytoprotection; D004789:Enzyme Activation; D005260:Female; D006107:Granulosa Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008875:Middle Aged; D010053:Ovary / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism*
C503049:BOK protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051020:bcl-X Protein; D053148:Caspase 3